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PubMed1996

Influence of fathers' social class on cardiovascular disease in middle-aged men.

BACKGROUND: The independent effect of early life circumstances on adult cardiovascular risk is still unresolved. We assessed the associations of father's social class with cardiovascular risk factors and with risk of ischaemic heart disease and stroke in adult life. METHODS: We did a longitudinal study of cardiovascular disease in 5934 men aged 40-59 years at enrollment. A cross-sectional measurement survey was done between 1978 and 1980 and a follow-up questionnaire was completed in 1992. The main endpoints were non-fatal myocardial infarction and stroke based on general practitioners' reports obtained between screening and 1992 and on recall of physician-diagnosed ischaemic heart disease in the 1992 questionnaire. FINDINGS: Father's social class was strongly associated with social class in adulthood (fathers' occupation was manual for 41.3% of professionals [I] vs 89.1% for unskilled manual workers [V]) and was significantly related to height (non-manual vs manual 175.4 cm [SE 0.2] vs 172.9 cm [0.1], p < 0.0001) and obesity (213 [14.1%] vs 804 [20.1%], p < 0.0001) irrespective of adult social class; no association was found with blood glucose (log, 1.69 [0.005] vs 1.70 [0.003], p = 0.22) or cholesterol (6.34 [0.03] vs 6.29 mmol/L [0.02], p = 0.16. Men whose fathers' social class was manual had significantly higher rates of non-fatal myocardial infarction (342/4006 vs 92/1510) and self-reported physician-diagnosed ischaemic heart disease (686/4006 vs 192/1510) than men whose fathers' social class was non-manual, even after adjustment for adult social class and other established risk factors (relative odds 1.3 [95% Cl 1.0-1.7], p < 0.05 and 1.3 [1.1-1.6], p < 0.01, respectively). The influence of father's social class on non-fatal myocardial infarction and ischaemic heart disease was only seen in men whose adult social class was non-manual. No association was seen between father's social class and non-fatal stroke. INTERPRETATION: Father's social class is strongly associated with adult social class. The higher risk of non-fatal myocardial infarction and self-reported physician-diagnosed ischaemic heart disease seen in men whose father's social class was manual suggests that socioeconomic status early in life has some persisting influence on ischaemic heart disease risk in adult life.

Adult↗

PubMed1998

Class differences in the food rules mothers impose on their children: a cross-national study.

Many studies indicate that children in middle-class families have healthier eating habits than children in lower class families. Class differences in food rules, which parents and especially mothers impose on their children, may underlie these social inequalities in food consumption. The present study uses education as a classifying variable and analyses whether mothers with higher education prescribe more "healthy" foodstuffs for their children and whether they restrict more "unhealthy" food items than less educated mothers. Moreover, the study examines whether higher class mothers consider health aspects more often and the preferences of their family members less often in their choice of food, and whether class differences in these considerations explain class differences in food rules. To answer these questions, questionnaires on the food practices of 849 women living in middle-class or lower class districts in Maastricht (the Netherlands), Liège (Belgium) and Aachen (Germany) were collected and analysed. The majority of mothers in each city prescribed primarily foods that were served at dinner like meat and vegetables, and most mothers limited their children's consumption of sweet foods, soft drinks and snacks. Higher class mothers restricted more foods, but prescribed as many food items as their lower class counterparts. Class differences in the number of restricted foods were partly, but not completely, explained by class differences in health and taste considerations. Despite national variations in dietary habits and possibly in the education of children, class differences in food rules and the explanatory power of health and taste considerations were comparable in the three cities.

Adolescent↗

PubMed1997

Herbst appliance treatment of Class II, division 2 malocclusions.

The purpose of this investigation was to analyze quantitatively the sagittal skeletal and dental changes that contribute to occlusal correction in Herbst treatment of 14 Class II, Division 2 malocclusions. Forty Class II, Division 1 Herbst subjects were used for comparison. Lateral head films from before and after Herbst treatment were analyzed, according to the method of Pancherz. The results revealed that all patients were treated to Class I or overcorrected Class I molar and edge-to-edge incisor relationships. The maxillary and mandibular skeletal changes were similar in both examination groups. In the Class II, Division 2 subjects, sagittal molar and overjet corrections amounted to an average of 5.9 mm and 3.1 mm, respectively. When comparing the Class II, Division 2 with the Class II, Division 1 subjects, overjet correction was, for natural reasons, significantly larger (p < 0.001) in the Class II, Division 1 subjects. In the subjects with Class II, Division 2 malocclusions, the upper incisors were proclined (mean = 3.0 mm), whereas in the subjects with Class II, Division 1 malocclusions, the incisors were retroclined (mean = 2.3 mm). The lower incisors were on the average proclined more (p < 0.05) in the Class II, Division 2 subjects (mean = 3.4 mm) than in the Class II, Division 1 subjects (mean = 2.4 mm). For sagittal molar correction, no differences in tooth movements were seen between the two malocclusions groups. In conclusion, it was found that the Herbst appliance is most effective in the therapy of Class II, Division 2 malocclusions. Proclination of the lower incisors during treatment (anchorage loss) is advantageous in this type of malocclusion.

Adolescent↗

PubMed2002

Influence of CD4 T cells and the source of major histocompatibility complex class II-restricted peptides on cytotoxic T-cell priming by dendritic cells.

We have previously reported that bone marrow derived dendritic cells (DC) pulsed with major histocompatibility complex (MHC) class I-restricted peptide efficiently prime a cytotoxic T lymphocyte (CTL) response in vivo. Here we assess the involvement of CD4(+) T cells in the induction of CD8(+) CTL by DC by testing the ability of class II-deficient (C2D) DC, class II mutant (Alpha beta mut) DC and autologous serum generated DC (AS DC) to present class I-restricted antigens in vitro and in vivo. DC generated from the bone marrow of class II knockout mice and transgenic mice expressing a mutant class II that can not bind CD4 were phenotypically similar to wild type (wt) DC, except with regard to MHC class II expression. The C2D and Alpha beta mut DC, though fully capable of presenting the class I-restricted ovalbumin (OVA) peptide to a T-cell hybridoma in vitro, failed to prime a CTL response in vivo. Restoration of class II expression on C2D DC allowed priming of a CTL response; thus, the defect in CTL priming was indeed caused by the absence of class II expression. Likewise, DC generated in autologous serum were unable to prime a CTL response as these DC only express 'self' class II epitopes and therefore would not activate syngeneic CD4(+) T cells. Addition of exogenous class II epitopes rescued the ability of AS DC to prime a CTL response. These observations provide convincing evidence that efficient CTL induction by DC in vivo requires concomitant presentation of class II epitopes for CD4(+) T-cell induction.

Animals↗

PubMed2006

Direct peptide-regulatable interactions between MHC class I molecules and tapasin.

Tapasin (Tpn) has been implicated in multiple steps of the MHC class I assembly pathway, but the mechanisms of function remain incompletely understood. Using purified proteins, we could demonstrate direct binding of Tpn to peptide-deficient forms of MHC class I molecules at physiological temperatures. Tpn also bound to M10.5, a pheromone receptor-associated MHC molecule that has an open and empty groove and that shares significant sequence identity with class I sequences. Two types of MHC class I-Tpn complexes were detectable in vitro depending on the input proteins; those depleted in beta(2)m, and those containing beta(2)m. Both were competent for subsequent assembly with peptides, but the latter complexes assembled more rapidly. Thus, the assembly rate of Tpn-associated class I was determined by the conditions under which Tpn-MHC class I complexes were induced. Peptide loading of class I inhibited Tpn-class I-binding interactions, and peptide-depletion enhanced binding. In combination with beta(2)m, certain peptides induced efficient dissociation of preformed Tpn-class I complexes. Together, these studies demonstrate direct Tpn-MHC class I interactions and preferential binding of empty MHC class I by Tpn, and that the Tpn-class I interaction is regulated by both beta(2)m and peptide. In cells, Tpn is likely to be a direct mediator of peptide-regulated binding and release of MHC class I from the TAP complex.

Animals↗

PubMed1996

Binding of H-2Kb-specific peptides to TAP and major histocompatibility complex class I in microsomes from wild-type, TAP1, and beta2-microglobulin mutant mice.

Major histocompatibility complex (MHC) class I molecules are trimolecular complexes consisting of a heavy chain (HC), beta2-microglobulin (beta2m), and a short peptide. Assembly of MHC class I molecules is thought to take place early during biosynthesis. Deficiency in either beta2m or the transporter associated with antigen processing (TAP) results in accumulation of class I molecules in the endoplasmic reticulum (ER). In this study, we have assessed peptide binding to TAP and MHC class I in purified microsomes derived from wild-type, TAP1(-/-), beta2m-/-, and TAP1/beta2m-/- mice using a cross-linkable H-2Kb-binding peptide. This enabled us to study the influence of an intact TAP complex and beta2m on peptide binding to MHC class I and to analyze the stepwise interaction of peptide with TAP and MHC class I molecules. Peptide bound both immature and mature (terminally glycosylated) class I molecules in intact as well as permeabilized microsomes from wild-type mice. Efficient peptide binding to immature class I molecules was also detected in permeabilized microsomes from TAP1(-/-) mice. In contrast, no peptide binding to beta2m-free HC was detected in permeabilized microsomes from beta2m-/- and TAP1/beta2m-/- mice. However, the addition of exogenous beta2m allowed peptide binding to class I in permeabilized beta2m-/- and TAP1/beta2m-/- microsomes. These results demonstrate that a preformed class I HC middle dotbeta2m heterodimer is necessary for efficient peptide binding under physiological conditions. The observed peptide binding to class I in permeabilized TAP1(-/-) microsomes further suggests that TAP1 is not required for peptide binding to class I in the ER. Finally, kinetic studies allowed the demonstration of a stepwise binding of peptide to TAP, subsequent translocation across the ER membrane, a step that required ATP hydrolysis, and binding of peptide to preformed class I HC.beta2m heterodimers.

Adenosine Triphosphate↗

PubMed1992

Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice.

Murine T cell responses to human class II major histocompatibility complex (MHC) molecules were shown to be a minimum of 20-70-fold lower than responses to allogeneic molecules. Transgenic mice expressing slightly below normal (75-95%) or very high (250-380%) cell surface levels of human CD4 were utilized to determine whether this was due to a species-specific interaction between murine CD4 and class II molecules. Human CD4 was shown to function in signal transduction events in murine T cells based on the ability of anti-human CD4 antibody to synergize with suboptimal doses of anti-murine CD3 antibody in stimulating T cell proliferation. In mice expressing lower levels of human CD4, T cell responses to human class II molecules were enhanced up to threefold, whereas allogeneic responses were unaltered. In mice expressing high levels of human CD4, responses to human class II molecules were enhanced at least 10-fold, whereas allogeneic responses were between one and three times the level of normal responses. The relatively greater enhancement of the response to human class II molecules in both lines argues for a preferential interaction between human CD4 and human class II molecules. In mice expressing lower levels of human CD4, responses to human class II molecules were blocked by antibodies to CD4 of either species, indicating participation by both molecules. In mice expressing high levels of human CD4, responses to both human and murine class II molecules were almost completely blocked with anti-human CD4 antibody, whereas anti-murine CD4 antibody had no effect. However, anti-murine CD4 continued to synergize with anti-CD3 in stimulating T cell proliferation in these mice. Thus, overexpression of human CD4 selectively impaired the ability of murine CD4 to assist in the process of antigen recognition. The ability of human CD4 to support a strong allogeneic response under these conditions indicates that this molecule can interact with murine class II molecules to a significant extent. Despite the fact that human CD4 appeared to be the only functional coreceptor in these mice, responses to human class II molecules were still much lower than those to murine class II alloantigens. This indicates that species-specific interactions between class II molecules and CD4 expressed on peripheral T cells are not sufficient to account for the low xenogeneic response and that intrinsic differences in T cell receptor structures or the need for species specificity in the interaction between CD4 and class II molecules during positive selection are also important.

Animals↗

PubMed1994

The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy.

Invariant chain (Ii) contributes in a number of distinct ways to the proper functioning of major histocompatibility complex (MHC) class II molecules. These include promoting effective association and folding of newly synthesized MHC class II alpha and beta subunits, increasing transit of assembled heterodimers out of the endoplasmic reticulum (ER), inhibiting class II peptide binding, and facilitating class II movement to or accumulation in endosomes/lysosomes. Although the cytoplasmic tail of Ii makes a key contribution to the endocytic localization of class II, the relationship between the structure of Ii and its other diverse functions remains unknown. We show here that two thirds of the lumenal segment of Ii can be eliminated without affecting its contributions to the secretory pathway events of class II folding, ER to Golgi transport, or inhibition of peptide binding. These same experiments reveal that a short (25 residue) contiguous internal segment of Ii (the CLIP region), frequently found associated with purified MHC class II molecules, is critical for all three functions. Together with other recent findings, these results raise the possibility that the contributions of Ii to the early postsynthetic behavior of class II may depend on its interaction with the class II binding site. This would be consistent with the intracellular behavior of unoccupied MHC class I and class II molecules as incompletely folded proteins and imply a related structural basis for the similar contributions of Ii to class II and of short peptides to class I assembly and transport.

Antigens, Differentiation, B-Lymphocyte↗

PubMed1998

The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes.

Nef, a regulatory protein of human and simian immunodeficiency viruses, downregulates cell surface expression of both class I MHC and CD4 molecules in T cells by accelerating their endocytosis. Fibroblasts were used to study alterations in the traffic of class I MHC complexes induced by Nef. We found that Nef downregulates class I MHC complexes by a novel mechanism involving the accumulation of endocytosed class I MHC in the trans-Golgi, where it colocalizes with the adaptor protein-1 complex (AP-1). This effect of Nef on class I MHC traffic requires the SH3 domain-binding surface and a cluster of acidic amino acid residues in Nef, both of which are also required for Nef to downregulate class I MHC surface expression and to alter signal transduction in T cells. Downregulation of class I MHC complexes from the surface of T cells also requires a tyrosine residue in the cytoplasmic domain of the class I MHC heavy chain molecule. The requirement of the same surfaces of the Nef molecule for downregulation of surface class I MHC complexes in T cells and for their accumulation in the trans-Golgi of fibroblasts indicates that the two effects of Nef involve similar interactions with the host cell machinery and involve a molecular mechanism regulating class I MHC traffic that is common for both of these cell types. Interestingly, the downregulation of class I MHC does not require the ability of Nef to colocalize with the adaptor protein-2 complex (AP-2). We showed previously that the ability of Nef to colocalize with AP-2 correlates with the ability of Nef to downregulate CD4 expression. Our observations indicate that Nef downregulates class I MHC and CD4 surface expression via different interactions with the protein sorting machinery, and link the sorting and signal transduction machineries in the regulation of class I MHC surface expression by Nef.

Adaptor Protein Complex alpha Subunits↗

PubMed1998

Negative signaling by anti-HLA class I antibodies is dependent upon two triggering events.

mAb with specificity for the alpha3 domain of HLA class I antigens, such as mAb TP25.99 and W6/32, are capable of inhibiting the proliferation of stimulated T cells in vitro by binding to their surface HLA class I antigens. The inhibitory potential of another HLA class I alpha3 domain-specific mAb, A1.4, was evaluated. In contrast to mAb TP25.99 and W6/32, which routinely inhibited superantigen (SEB) stimulation of T cells by >90%, mAb A1.4 at equivalent concentrations demonstrated only 20-50% inhibition. Univalent Fab fragments of all three mAb lacked inhibitory activity. Interestingly, however, by combining univalent W6/32 (or TP25.99) Fab fragments with intact, bivalent mAb A1.4 (at a non-inhibitory, sub-threshold concentration of 1 microg/ml), significant inhibition of SEB-driven T cell proliferation was obtained. Inhibition by the anti-HLA class I mAb W6/32 and TP25.99 was evident even when SEB was used in conjunction with paraformaldehyde-fixed HLA class I-, class II+ Daudi cells, suggesting that the inhibitory activity of these mAb results from direct HLA class I epitope engagement on the T cell. These findings suggest that effective antibody-mediated induction of the HLA class I inhibitory pathway within T cells is dependent upon two separable molecular triggers at the T cell surface. The first can be delivered by univalent mAb derivatives that engage one or more critical HLA class I epitope(s). The second requires intact mAb, though seems to be less selective as to the HLA class I specificity. This model may explain why some, but not all, anti-HLA class I mAb are inhibitory when used singly. Achieving synergies between a wider array of anti-HLA class I mAb and their derivatives may provide a path for more effectively tapping into the HLA class I inhibitory pathway in a therapeutic context.

Animals↗

PubMed2001

Assembly of tapasin-associated MHC class I in the absence of the transporter associated with antigen processing (TAP).

The assembly of MHC class I molecules is regulated by a multi-protein complex in the endoplasmic reticules (ER) termed the loading complex. Tapasin is suggested to be one of the molecules forming this complex on the basis of its interaction with both the transporter associated with antigen processing (TAP) and MHC class I molecules. To address whether TAP is indispensable for the processing of the assembly of tapasin-associated MHC class I molecules, we studied the association of MHC class I molecules with tapasin, the assembly of tapasin-associated MHC class I with peptides and the peptide-mediated dissociation of MHC class I from tapasin in TAP-mutant T2 cells. In the absence of TAP, MHC class I heavy chain and beta(2)-microglobulin dimers were found to be properly associated with tapasin. The stable MHC class I dimer was required for its association with tapasin in the ER. In the absence of TAP, tapasin retained MHC class I molecules much longer in the ER than in the presence of TAP. This low off-rate of MHC class I from tapasin was due to the absence of high-affinity peptides in the ER of TAP-mutant cells but not to the absence of TAP per se. The introduction of peptides into permeabilized microsomes of TAP-mutant cells led to effective loading of the peptides onto tapasin-associated MHC class I and to the subsequent dissociation of MHC class I from tapasin. These results demonstrate that regulation of the assembly of tapasin-associated MHC class I is independent of the interaction of tapasin with TAP, but is dependent upon the peptides transported by TAP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Major histocompatibility class II expression in the normal canine cornea and in canine chronic superficial keratitis.

OBJECTIVE: To compare the expression of major histocompatibility complex (MHC) class II antigen in the corneas of normal dogs and dogs affected with chronic superficial keratitis (CSK). METHODS: MHC class II expression was determined in frozen sections of normal canine cornea and cornea from lesions of CSK by immunohistochemistry using a monoclonal antibody directed against the canine MHC class II molecule. Langerhans cell phenotype was determined morphologically and by histochemical determination of ATPase activity. To determine the influence of gamma interferon on expression of MHC class II molecules by corneal cells, corneal explants were cultured with the cytokine and MHC class II expression determined as above. RESULTS: Numerous MHC class II-expressing cells were demonstrated within the stroma and epithelium of the normal corneal limbus and conjunctival epithelium while very little MHC class II expression was detected in the central region of normal canine cornea. In limbal and conjunctival epithelium, cells expressing MHC class II antigen showed ATPase activity, suggesting that they were Langerhans cells. Corneas from dogs with CSK showed MHC class II expression associated with stromal cells, some of which exhibited a dendritic morphology while most were lymphocytic. Corneal epithelial cells within the lesion also aberrantly expressed MHC class II. Corneal explants expressed MHC class II to varying degrees after differing periods of incubation with the cytokine gamma interferon. CONCLUSIONS: While the normal central cornea has little MHC class II expression, aberrant expression occurs in CSK, associated with secretion of gamma interferon by infiltrating CD4-expressing lymphocytes. Although this change is likely to be a secondary feature of the CSK lesion, increased MHC class II expression may play a part in perpetuating the corneal inflammation seen in the disease.

Adenosine Triphosphatases↗

PubMed1984

Immunologic characterization of MHC recombinant swine: role of class I and II antigens in in vitro immune responses.

A recombinant haplotype between the class I and class II major histocompatibility loci of inbred miniature swine has made it possible to study the role of the corresponding antigens in in vitro and in vivo immune responses. Before examining the effects of selective SLA locus matching on allograft survival, it was deemed necessary to determine the corresponding effects on in vitro parameters of immunity. The results presented in this paper indicate that: (1) a difference at the class II loci was required for a maximal proliferative response; (2) class I antigen differences alone led to a slight proliferative response which depended on the haplotype combination used; (3) in cell-mediated cytoxicity assays, the class I antigens were found to be the primary targets for lysis. Although optimal CTL generation required the presence of both class I and class II antigen differences, CTL were sometimes generated in the absence of a known class II difference. The weak, intermittent cytotoxicity seen in these cultures of class II matched cells could be augmented by the addition of third party, class I matched, class II mismatched, stimulator cells. Taken together, these data provide evidence for the conservation of function of antigen class between species. They also provide further evidence for the two-signal hypothesis of CTL generation. Thus, MHC recombinant swine provide a model for the study of the effect of antigen class on in vitro and in vivo immunobiology.

Animals↗

PubMed2006

Inhibition of heavy chain and beta2-microglobulin synthesis as a mechanism of major histocompatibility complex class I downregulation during Epstein-Barr virus replication.

The mechanisms of major histocompatibility complex (MHC) class I downregulation during Epstein-Barr virus (EBV) replication are not well characterized. Here we show that in several cell lines infected with a recombinant EBV strain encoding green fluorescent protein (GFP), the virus lytic cycle coincides with GFP expression, which thus can be used as a marker of virus replication. EBV replication resulted in downregulation of MHC class II and all classical MHC class I alleles independently of viral DNA synthesis or late gene expression. Although assembled MHC class I complexes, the total pool of heavy chains, and beta2-microglobulin (beta2m) were significantly downregulated, free class I heavy chains were stabilized at the surface of cells replicating EBV. Calnexin expression was increased in GFP+ cells, and calnexin and calreticulin accumulated at the cell surface that could contribute to the stabilization of class I heavy chains. Decreased expression levels of another chaperone, ERp57, and TAP2, a transporter associated with antigen processing and presentation, correlated with delayed kinetics of MHC class I maturation. Levels of both class I heavy chain and beta2m mRNA were reduced, and metabolic labeling experiments demonstrated a very low rate of class I heavy chain synthesis in lytically infected cells. MHC class I and MHC class II downregulation was mimicked by pharmacological inhibition of protein synthesis in latently infected cells. Our data suggest that although several mechanisms may contribute to MHC class I downregulation in the course of EBV replication, inhibition of MHC class I synthesis plays the primary role in the process.

Cell Line, Transformed↗

PubMed2004

[Inequalities in health related to social class in women. What is the effect of the measure used?].

Classical theories of social stratification share the assumption that the family is the unit of stratification, using the man's occupation as a measure of social class. These theories were criticized by feminism, which claimed that women were not visible in class analysis. The present article aims firstly to review measurement of women's social class, secondly to review studies on the impact of different measures of social class on inequalities in health among women, and thirdly to illustrate the differences among alternative measures, using data from the Barcelona Health Interview Survey 2000 as an example. There are few studies analyzing inequalities in health among women that take into account several measures of social class; most studies have been performed in the United Kingdom, although some studies have been conducted in other countries. Typically, these studies compare several social class indicators: the conventional social class measure, which uses the husband's occupation or that of the head of household (a household measure); the individual social class measure, which uses women's occupation, and the dominant social class measure, which allocates an individual the highest social class within a household (also a household measure). The impact of the various measures on inequalities in health varies according to the study performed, but is usually greater with the conventional and dominant approaches. Data from the Health Interview Survey of Barcelona 2000 show the existence of inequalities in health using these three approaches, with varied impact according to the health indicators used and women's characteristics.The dominant social class measure has several advantages: it is gender-blind and is not sexist. When the dominant social class is a less privileged class (i.e. manual laborer) it means that both partners have an occupation equal to or lower than this measure. Finally, this indicator is easily obtained.

Female↗

PubMed2002

Social class and heart disease mortality among African Americans.

The purpose of the present study was to examine variation in heart disease death rates by the social class of decedents. The term, "social class" refers to a complex set of phenomena such as control over economic resources, social status, and power relative to others in society. The target population for this study was African-American adults aged 35-74 years old who resided in the United States during the years 1996-1997. As a proxy for social class, we examined 5 levels of educational attainment: 0-8 years of school completed (Social Class I), 9-11 years of school completed (Social Class II), high school graduate/12 years of school completed (Social Class III), some college completed (Social Class IV), and college degree completed (Social Class V). Older age, male gender, and lower social class were all independently associated with higher heart disease death rates. For all ages, more disadvantaged social classes had a higher risk of heart disease mortality. The highest relative risks were found for Social Classes I and II among the younger age groups. Many of the "prerequisites" for the "heart healthy lifestyle" are predicated on the benefits of a privileged social class position. For African Americans, there are the additional stressors of segregation, exclusion, and discrimination to overcome, as well as the cumulative physiological toll of lifetime resistance to various forms of racism. For many African Americans in disadvantaged social class positions, the obstacles to reducing the risk for heart disease are very difficult to overcome.

Adult↗

PubMedDate not supplied

Tumour MHC class I downregulation and immunotherapy (Review).

MHC class I downregulation is an important mechanism of tumour escape from T cell-mediated immune responses. Approximately 40-90% of human tumours derived from various MHC class I+ tissues were reported to be MHC class I deficient. Decreased or absent MHC class I expression is frequently associated with the invasive and metastatic tumour phenotype. Altered MHC class I antigen expression involves total loss, loss of haplotype, locus downregulation, allelic loss or downregulation, and combinations. Description of partial or complete losses of MHC class I molecules in tumour cells as mechanisms of immune escape often fails to consider an increased susceptibility to NK cell-mediated lysis, which is a direct consequence of such losses. A low MHC class I level favours NK cells as effectors, whereas a high level of MHC class I favours T cells as effectors. The microheterogeneity of MHC class I expression in tumour cell populations, the balance of the MHC-restricted and MHC-unrestricted defence as well as the selective pressure of antigen-specific (CTL) and antigen non-specific (NK) effector mechanisms decide the final outcome of the MHC class I expression in the primary tumour and its metastases as well as the final outcome of the tumour defence reaction. Despite the MHC class I molecule deficiency and the resulting absence of the CD8+ T cell-mediated immunity, the tumour hosts were found to be capable of being immunized against MHC class I- tumours. The purpose of this review is to discuss the positive results of MHC class I- tumour treatment obtained with immunomodulatory cytokines and tumour vaccines, as well as the prospects and limitations of such therapy.

Alleles↗

PubMed1988

Expression of class I HLA genes by trophoblast cells. Analysis by in situ hybridization.

Evaluation of trophoblast cells by immunohistology has shown that subpopulations of trophoblast cells express class I HLA differently from one another and differently from embryonic and adult cells. Placental syncytial trophoblast does not express detectable levels of class I HLA; chorion membrane cytotrophoblasts bind one mAb to monomorphic determinants of class I Ag, W6/32, but not a second, 61D2. In the present study, sections of normal term placentae and matching extraplacental membranes were evaluated by in situ hybridization procedures for cells containing class I HLA mRNA using pHLA1.1, which is complementary to HLA-B. Class I Ag expression was identified by immunohistology using two mAb to class I HLA (W6/32, 61D2) and the mAb 4E to identify HLA-B. Placental syncytial trophoblast contained low to undetectable levels of class I mRNA and failed to bind all three mAb. Chorion membrane cytotrophoblast cells contained moderate levels of class I HLA mRNA and were positive with the mAb W6/32 but were negative with 61D2 and 4E. In adjacent tissues, fetal mesenchymal cells and maternal decidual cells contained high levels of class I mRNA and were positive with all three mAb. The results suggest that syncytial trophoblast may not express class I HLA because of low steady-state levels of class I HLA mRNA. In contrast, chorionic cytotrophoblast cells may express truncated versions of class I HLA or nonclassical HLA-A,B,C-like Ag. Regulation of the expression of class I HLA gene products may be essential to the development of a satisfactory immunologic relationship between the mother and her semiallogeneic fetus during pregnancy.

Antibodies, Monoclonal↗