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At least 1,027 records · Page 57Linked to original sources
PubMed1994

Analysis of the MHC class II encoded components of the HLA class I antigen processing pathway in ankylosing spondylitis.

OBJECTIVES: The evaluation of the role of polymorphism within the class II encoded antigen processing genes, LMP2 and TAP, in susceptibility to ankylosing spondylitis (AS). METHODS: Eighty five patients with ankylosing spondylitis, 35 B27 positive healthy controls, and 55 unrelated healthy controls were studied. TAP1 and TAP2 alleles were assigned by ARMS PCR, and LMP2 alleles were assigned by restriction enzyme digestion of a PCR product. RESULTS: The TAP1C allele was increased in the AS group (6%) compared with random controls (1%), p = 0.03 and TAP2E was increased in AS (3.5%) compared with random controls (0%), p = 0.05. However, the frequencies of these alleles were also increased in B27 matched controls. There were no differences in LMP2 allele or genotype frequencies between AS and either of the control groups. Partitioning of patients according to presence or absence of uveitis did not reveal any significant associations. CONCLUSIONS: Increases of the minor TAP alleles, 1C and 2E, in AS reflect linkage disequilibrium between these alleles and HLA-B27. Polymorphism of the class I antigen processing pathway does not contribute significantly to AS susceptibility nor to the development of anterior uveitis associated with AS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Association of HLA class I and class II antigens with rheumatic fever in a Turkish population.

The distribution of class I and class II HLA antigens of 100 Turkish patients with rheumatic fever, 77 of whom had cardiac involvement, was examined. We compared the results with a control group of identical origin. The frequency of HLA A10 and HLA B35 antigens were found significantly higher in patients with rheumatic fever (p < 0.05, p < 0.01, respectively). The frequency of HLA A10 and HLA DRw11 in patients with cardiac involvement were significantly higher than in those without cardiac involvement (p < 0.05, p < 0.01, respectively). On the other hand, HLA Cw2 antigen frequency was found significantly higher in patients without cardiac involvement than in those with rheumatic heart disease (p < 0.05). We support the concept that rheumatic fever is an immunological reaction to group A, beta hemolytic streptococci in individuals who have genetic predisposition.

Acute Disease↗
PubMed2003

Associations of Moyamoya patients with HLA class I and class II alleles in the Korean population.

Moyamoya disease is characterized by progressive cerebrovascular occlusion at the peripheral internal carotid artery and development of abnormal collateral circulation at the cerebral basal region. Although abnormal thrombogenesis, inflammation and autoimmune process might be involved in the etiology, the genetic pathogenesis of Moyamoya disease is still unknown. To evaluate the association of Moyamoya disease with HLA alleles in the Korean population, we investigated HLA class I and class II alleles in 28 Moyamoya patients and 198 unrelated healthy controls. The frequency of HLA-B35 allele was significantly increased in the patients compared to the controls (32.1% vs. 10.1%, RR=4.2, p<0.008). Further analysis of HLA-B35 on onset age and sex showed that this allele was significantly increased compared to the controls in both late-onset and female group. Especially, HLA-B35 was the most significantly increased in female of late-onset group compared to the controls. These results suggest that HLA-B35 may be an useful genetic marker for Moyamoya disease, and particularly in females of late onset group in the Korean population.

Adolescent↗
PubMed1999

Soluble HLA class I, HLA class II, and Fas ligand in blood components: a possible key to explain the immunomodulatory effects of allogeneic blood transfusions.

The immunomodulatory effect of allogeneic blood transfusions (ABT) has been known for many years. However, a complete understanding of the effects of ABT on the recipient's immune system has remained elusive. Soluble HLA class I (sHLA-I), HLA class II (sHLA-II), and Fas ligand (sFasL) molecules may play immunoregulatory roles. We determined by double-determinant immunoenzymatic assay (DDIA) sHLA-I, sHLA-II, and sFasL concentrations in different blood components. sHLA-I and sFasL levels in red blood cells (RBCs) stored for up to 30 days and in random-donor platelets are significantly (P <.001) higher than in other blood components and their amount is proportionate to the number of residual donor leukocytes and to the length of storage. Blood components with high sHLA-I and sFasL levels play immunoregulatory roles in vitro as in allogeneic mixed lymphocyte responses (MLR) and antigen-specific cytotoxic T-cell (CTL) activity, and induce apoptosis in Fas-positive cells. These data suggest that soluble molecules in blood components are functional. If these results are paralleled in vivo, they should be taken into account in transfusion practice. Blood components that can cause immunosuppression should be chosen to induce transplantation tolerance, whereas blood components that lack immunosuppressive effects should be preferred to reduce the risk of postoperative complications and cancer recurrence.

Adjuvants, Immunologic↗
PubMed2002

Association of psoriasis vulgaris with HLA class I and class II antigens in the Turkish population, according to the age at onset.

BACKGROUND: Association of psoriasis vulgaris with HLA antigens reference to age at onset has been reported in different racial or ethnic populations. OBJECTIVE: Our purpose was to determine the distribution of HLA markers in the Turkish population according to the age at onset of the psoriasis vulgaris. METHODS: HLA class I and class II antigens were performed by serologic methods in a group of 100 Turkish patients with psoriasis and 201 control subjects. Patients with psoriasis were subdivided into two groups based on age at onset (below or above 40 years of age) and family history. RESULTS: The frequency of HLA A30, Cw3, Cw6, DR7, DR14, DQ8, and DQ9 antigens were significantly increased in the Turkish psoriatic patients whereas HLA A66, Cw2, Cw4 and DR11 were found to be negatively associated with psoriasis. However, there were striking differences in HLA antigens according to the age at onset of the disease. Type I, early onset was associated with a high frequency of A30, B50, Cw6 and DR7 antigens whereas patients with type II, late onset had an increased frequency of Cw7. CONCLUSIONS: We conclude that psoriasis is probably a genetically determined disease and suggest that HLA-Cw6 antigen seems to associate commonly with early onset of psoriasis in Turkish patients.

Adolescent↗
PubMed1991

The importance of class I and class II HLA in cadaveric renal transplantation.

The importance of avoiding mismatches (MM) at Class I and Class II HLA antigens in cyclosporine-treated renal allograft patients is controversial. In order to assess the role of HLA, 200 consecutive cadaveric renal allografts over a 4-year period were analysed. All patients received cyclosporine/predinisone immunosuppression and 75% were induced with ALG. Minimum follow-up period was one year. HLA A, B, DR, DQ, and DRw52/53 typing were available on 77-100% of allografts. A beneficial effect was noted at the HLA A locus. One-year survival was 87.2% in the 0 and 1 HLA A MM group combined vs 73.8% in the 2 HLA A MM group (p less than 0.05). The mean creatinine level at one year was also lower in the 0 plus 1 MM vs 2 MM group: 152.8 mumol/L vs 184.8 mumol/L, respectively (p less than 0.05). Significantly fewer rejection episodes occurred in the 0 and 1 HLA DQ MM group combined vs the 2 MM group. Steroid-resistant rejection episodes (SRRE) were not associated with the number of HLA MM. Patients who had an SRRE had significantly higher mean current and historical peak panel reactive antibodies (PRA) than patients who did not have SRRE. These results indicate that avoiding mismatches at the HLA A locus may improve renal allograft survival, and matching at HLA DQ may predispose patients to a more quiescent post-transplant course. The degree of preoperative sensitization may be an important etiologic factor in SRRE.

Cadaver↗
PubMed1990

Electromyographic findings in Class II division 2 and Class III malocclusions.

Electromyography of masticatory muscles has proved useful for the functional study of occlusal dysfunctions. We employed this technique to study the activity of masseter and temporal muscles of 6 subjects with Class II division 2 malocclusion and 7 subjects with Class III malocclusion. Significant differences of masticatory muscles activity during mastication and swallowing were observed between the two groups. We hypothesize that the change of the activity of masticatory muscles might influence the clinical presentation of malocclusion.

Adult↗
PubMed1988

Lymphokine-independent induction of macrophage membrane IL-1 by autoreactive T cells recognizing either class I or class II MHC determinants.

Here we report that autoreactive T cell clones and T cell hybridomas that recognize class I or class II MHC determinants can induce IL-1 expression on cultured macrophages in an MHC-restricted manner. This genetic restriction of membrane IL-1 (mIL-1) induction is not absolute, however; it is manifest only in macrophages that have been cultured for several days before stimulation. Macrophages that are evaluated within 24 h after adherence display a basal level of mIL-1, and the T cell-induced augmentation of basal mIL-1 expression is not MHC-restricted. It appears that T cells of both Th1 and Th2 type have the capacity to induce mIL-1, suggesting that this function is not limited to the T cell subset (Th2) that is able to use IL-1. Most importantly, the ability of T cells to induce IL-1 on macrophages seems to occur by virtue of direct cellular interactions, and is independent of lymphokine secretion. The induction event is rapid enough (2 to 4 h) to allow T cells to interact with both antigen and IL-1 during the initial T cell/macrophage contact. These findings thus reveal an efficient mechanism for the induction of IL-1 during Ag presentation to T cells.

Animals↗
PubMed1994

Soluble HLA class II concentrations in normal individuals and transplant recipients. Comparison with soluble HLA class I concentrations.

We developed an ELISA to quantify soluble HLA class II (S-HLA-II) in 702 sera obtained from normal subjects, patients with end-stage renal disease, and recipients of renal, hepatic, and cardiac transplants. Concentrations of S-HLA-II were detectable in 124 of 126 normal individuals. The distribution of normal values described a monophasic curve with a skewed distribution. In transplant recipients, there were no differences between preoperative and posttransplant values, but values in liver patients were significantly higher than in kidney patients, and values for heart patients were lowest of all groups. There were periodic variations in concentrations in individual patients, but these were unrelated to rejection, infection, or any other apparent clinical event. S-HLA-II was consistently present in the urine. All of these observations contrast with previous observations concerning soluble HLA class I (S-HLA-I) molecules, which were almost the precise reverse. It seems likely that these clear differences in S-HLA-II and S-HLA-I concentrations relate to different physiologic processes in either production, function, or elimination.

Graft Rejection↗
PubMedDate not supplied

Heterogeneity of the alpha-interferon-mediated overexpression of class-I and class-II major histocompatibility complex molecules in primary cultured cancer cells.

Human alpha- and gamma-interferons (IFNs) have the capability of enhancing the expression of major histocompatibility complex-class I and class II (MHC-I and MHC-II) as well as other surface tumor associated antigens (TAA) on cancer cell lines. This capability, associated to the anti-proliferative effect observed both in vitro and in vivo, was the basis of the extended use of IFN in cancer patients. Despite the great expectations, several solid neoplasms resulted resistant to treatment with IFNs. In order to analyze the actual effects of IFNs on cancer, we treated primary cultures of different histotypes of cancer cell, which are well known to differ significantly from established cell lines, with escalating doses of alpha-IFN. In this paper, we demonstrate that a variable proportion of culture was able to potentiate the expression of MCH-I and MCH-II molecules on the surface. This finding suggests that a clear functional heterogeneity was present in primary cultures of cancer cells, that strictly reflected the in vivo situation. In addition, it is of note that in some histotypes, "natural" lymphoblastoid alpha-IFN was more effective than recombinant human alpha-IFN in the induction of this capability.

Histocompatibility Antigens Class I↗
PubMed1993

Phorbol myristate acetate-differentiated THP-1 cells display increased levels of MHC class I and class II mRNA and interferon-gamma-inducible tumoricidal activity.

The protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and mezerein induce differentiation of human monocytic leukemia (THP-1) cells along the monocyte/macrophage pathway of development. The differentiated cells express many important macrophage functions including phagocytosis and the secretion of immunomodulatory cytokines. Mezerein-differentiated THP-1 cells secrete interleukin-1 beta as well as a tumor cell growth inhibitory factor whose basal level is increased in response to interferon-gamma. However, tumoricidal, as opposed to tumoristatic, activity of differentiated THP-1 has not been documented. We report herein that PMA-differentiated THP-1 cells (PD/THP-1) contain elevated levels of MHC class I and class II mRNAs even in the absence of activating factors, and kill HT-29 human colon carcinoma cells when stimulated with recombinant human interferon-gamma. These two characteristics are important components of the macrophage phenotype. The results presented in this study extend previous observations on THP-1 cells by demonstrating that PD/THP-1 cells display a critical, immunologically relevant macrophage function, and therefore, enhance the utility of THP-1 as a model for the in vitro study of immunomodulatory drugs and macrophage-mediated cytocidal processes.

Antigens, Neoplasm↗
PubMed1997

Molecular typing of HLA class I and class II antigens in Indian kala-azar patients.

HLA has been shown to be associated with many diseases. To find out whether host genetic factors like the HLA are involved in susceptibility to kala-azar (visceral leishmaniasis) in India, we formulated an association study with genetically related controls. All samples were typed by PCR SSOP (sequence specific oligonucleotide probes) for HLA class I (A and B) and class II (DR) antigens. The test of association we used was the transmission disequilibrium test (TDT). No significant evidence for association with any of the three HLA loci was obtained.

Disease Susceptibility↗
PubMed1999

Murine T lymphocytes incapable of producing macrophage inhibitory protein-1 are impaired in causing graft-versus-host disease across a class I but not class II major histocompatibility complex barrier.

The routine use of bone marrow transplantation is limited by the occurrence of acute and chronic graft-versus-host disease (GVHD). Current approaches to decreasing the occurrence of GVHD after allogeneic transplantation use T-cell depletion, use immunosuppressive agents, or block costimulatory molecule function. The role of proteins in the recruitment of alloreactive lymphocytes has not been well characterized. Chemokines are a large family of proteins that mediate recruitment of mononuclear cells in vitro and in vivo. To investigate the role of T-cell production of the chemokine macrophage inhibitory protein-1 (MIP-1) in the occurrence of GVHD, splenocytes either from wild-type or from MIP-1-/- mice were administered to class I (B6.C-H2(bm1)) and class II disparate mice (B6-C-H2(bm12)). The incidence and severity of GVHD was markedly reduced in bm1 mice receiving splenocytes from MIP-1-/- mice as compared with mice receiving wild-type splenocytes. Bm1 mice receiving MIP-1-/- splenocytes had significantly less weight loss and markedly reduced inflammatory responses in the lung and liver than mice receiving C57BL/6 splenocytes. Bm1 mice receiving MIP-1-/- splenocytes had a markedly decreased production of antichromatin autoantibodies and impaired generation of bm1-specific T lymphocytes versus wild-type mice. However, MIP-1-/- splenocytes easily induced GVHD when administered to bm12 mice. This data show that blockade of chemokine production or function may provide a new approach to the prevention or treatment of GVHD but that chemokines that recruit both CD4(+) and CD8(+) lymphocytes may need to be targeted.

Animals↗
PubMed1991

Vaccination of class I major histocompatibility complex (MHC)-restricted murine CD8+ cytotoxic T lymphocytes towards soluble antigens: immunostimulating-ovalbumin complexes enter the class I MHC-restricted antigen pathway and allow sensitization against the immunodominant peptide.

In vivo induction of anti-ovalbumin (OVA) cytotoxic T cell responses was brought about in an MHC class I-restricted fashion by immunizing H-2b mice with OVA in immunostimulating complexes (ISCOM). ISCOM formation with the hydrophilic soluble protein OVA was achieved upon unmasking hydrophobic protein domains by treatment at low pH values. The effector cells induced were MHC restricted, specific for the immunodominant peptide of OVA (258-276), and expressed the CD8+ CD4- phenotype. These results suggest that ISCOM-based vaccines may be useful to direct hydrophilic soluble antigens into the MHC class I presentation pathway in order to vaccinate CD8+ T lymphocytes.

Animals↗
PubMed1992

Modulation of restricted class II T cell responses by peptides derived from self class II molecule.

We have explored the possibility of using peptides derived from a major histocompatibility complex (MHC) class II (I-Ab) molecule to modulate I-Ab-restricted T cell responses. Six peptides spanning the polymorphic regions of I-Ab were analyzed for competitive binding to the I-Ab molecule, and for efficacies in blocking I-Ab-specific T cell response. Only PB1 (residues 75-91 of beta chain) bound the I-Ab molecule with high affinity. When these MHC-derived peptides were administered simultaneously with antigen, PB1 effectively inhibited I-Ab-restricted T cell responses as well as another peptide PB2 (residues 59-78 of beta chain). PB2 inhibited specific T cell response only when it was administered simultaneously with antigen. Since PB2 is a weak binder of I-Ab, an additional mechanism must account for its inhibitory activity. Both PB1 and PB2 peptides elicited specific T cell responses, indicating that these peptides were not tolerogenic in syngeneic mice. However, the induction of T cells in response to PB1 and PB2 did not increase reactivity to I-Ab. MHC class II-derived peptides thus can be used to regulate T cell responses without the risk of autoreactivity.

Amino Acid Sequence↗
PubMed1994

Preformed purified peptide/major histocompatibility class I complexes are potent stimulators of class I-restricted T cell hybridomas.

A panel of antigen-specific, major histocompatibility complex class I-restricted T cell hybridomas has been generated to examine the capacity of peptide/class I complexes to stimulate T cells at the molecular level. Peptide/class I complexes were generated in detergent solution, purified and quantitated. Latex particles were subsequently coated with known amounts of preformed complexes and used to stimulate the T cell hybridomas. Stimulation was specific, i.e. only the appropriate peptide/class I combination were stimulatory, and quite sensitive, i.e. as little as 300 complexes per bead could be detected by the T cells. Preformed complexes were about 500,000 times more potent than free peptide in terms of T cell stimulation, demonstrating the physiological relevancy of the biochemically generated complexes. Surprisingly, the majority (including the most sensitive of the hybridomas) had lost CD8 expression, suggesting that antigen-specific stimulation of class I-restricted T cell hybridomas, as assessed by IL-2 release, does not depend on CD8.

Amino Acid Sequence↗
PubMed1997

Fetal and neonatal NK1.1+ Ly-49- cells can distinguish between major histocompatibility complex class I(hi) and class I(lo) target cells: evidence for a Ly-49-independent negative signaling receptor.

Natural killer (NK) cell function is regulated by both positive and negative signaling receptors. In adult splenic NK cells, negative signaling has been shown to be mediated by the Ly-49 family receptors. NK1.1- 2B4+ CD3- cells that are phenotypically and functionally similar to adult splenic NK cells can be derived from murine fetal liver and thymus. These cells do not express any known Ly-49 molecules on their surface nor do they contain the known Ly-49 transcripts. Surface expression of Ly-49 molecules is first detected on splenic NK1.1+ cells 4-6 days after birth. Despite the absence of these negative signaling receptors, fetal and neonatal Ly-49- NK cells lyse TAP-/- , major histocompatibility complex (MHC) class I(lo) but not TAP+/+, MHC class I(hi) target cells. This suggests that fetal and neonatal NK cells express negative signaling receptors other than Ly-49 molecules.

Animals↗