SEARCH · PubMed Health

Results for “Class”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed1999

Evolution of HLA-class I compared to HLA-class II polymorphism in Terena, a South-American Indian tribe.

We have studied the HLA alleles of 60 unrelated healthy Terena and 10 Terena families. They are members of an isolated Brazilian tribe located in Mato Grosso do Sul (South Central Brazil). Six novel alleles were found in this population: HLA-A*0219 (gf = 0.02), A*0222 (gf = 0.15), HLA-B* 3520 (gf = 0.01), B*3521 (gf = 0.03), B*3912 (gf = 0.03) and B*4803 (gf = 0.16). Five of the six novel alleles differ from their putative progenitors by amino acid replacements in residues that contribute to the pockets of the peptide-binding site. Many of the variants defined by molecular methods were not identified correctly by serological typing. We calculated heterozygosity values (H) for HLA-A, -B, -C, DRB1, DQB1 and DPB . The highest values were observed at the HLA-B locus, followed by HLA-A, -DRB1 and DQB1. Residue positions 9, 24, 45, 62, 67, 95, 114, 116, 156, and 163 of HLA class I showed heterozygosity values greater than 0.50. Nine of them contribute to the peptide-binding specificity pockets and one to the T cell receptor binding site. If HLA antigens are useful for defense against pathogenic agents, heterozygosity would offer an advantage by allowing binding of a larger repertoire of peptides to the class I molecules. Individuals that are heterozygous at these positions would probably have a wider repertoire of peptide presentation to T cells. The observed results including the presence of novel alleles in the class I HLA loci suggest a functionally significant, more rapid evolution of class I compared to class II loci in this South American isolated population.

Alleles↗

PubMed2002

Infection of mouse bone marrow-derived dendritic cells with recombinant adenovirus vectors leads to presentation of encoded antigen by both MHC class I and class II molecules-potential benefits in vaccine design.

Dendritic cells (DCs) are highly specialised antigen-presenting cells (APCs) that are essential for the initiation and modulation of T cell-mediated immune responses. In order to induce effective CTL responses against most infections and tumours, DCs must prime both CD4(+) and CD8(+) antigen-specific T cells. It is, therefore, important in vaccine design to produce antigen-delivery systems that lead to the simultaneous presentation of multiple histocompatibility complex (MHC) class I- and class II-restricted antigenic peptides by DCs. In this study, the infection of immature mouse bone marrow-derived DCs (BMDCs) with recombinant adenovirus (rAd) vectors led to a marked upregulation of surface costimulatory molecules, IL-12 p40 production and capacity to stimulate both allogeneic and antigen-specific T cells. Furthermore, infection of immature and mature BMDCs with a rAd encoding chicken ovalbumin (OVA) led to presentation of the antigen to TCR-transgenic OVA-specific CD4(+) and CD8(+) T cells. In addition, the activation state of responding CD8(+) T cells was further amplified if they recognised antigen on rAd-transduced BMDCs in the presence of antigen-specific CD4(+) T cells. The results suggest that rAd-encoded OVA protein is secreted by BMDCs, taken up by endocytosis and presented in association with MHC class II molecules for activation of OVA-specific CD4(+) T cells. Consequently, rAd-transduced immature BMDCs become better stimulators of antigen-specific CD4(+) T cells than rAd-infected mature BMDCs. Taken together, these data have important implications for vaccine design, and suggest that infection of immature DCs with rAd encoding MHC class I and class II-restricted T cell epitopes could be an efficient means of inducing effective immune responses.

Adenoviridae↗

PubMed1997

MHC class I and class II structures.

The basic structures of MHC class I and class II molecules are now well established. Over the past twelve months structural data on MHC class I molecules have provided details of the peptide binding groove for a number of alleles and have elaborated the mechanisms that allow binding of a range of peptides. Recent MHC class II structures have illustrated the mode of peptide binding both in mature complexes and in the MHC class II complex with a fragment of invariant chain (CLIP) during maturation.

Animals↗

PubMed2003

Effects of extraction and nonextraction treatment on class I and class II subjects.

This study aims to examine the profile as well as the dentoalveolar and skeletal effects of extraction or nonextraction treatment in a wide range of patients including Class I and Class II, division 1 cases. Results achieved with extraction and nonextraction modalities have also been compared. The study was performed on pretreatment and posttreatment lateral cephalograms of 87 orthodontic patients. There were no significant differences between the pretreatment values of extraction and nonextraction Class I groups, whereas SN-GoGn (degrees), maxillary incisor to A-Po (degrees), mandibular incisor to A-Po (mm), Co-Gn (mm), overjet (mm), and overbite (mm) measurements of extraction Class II group were significantly higher before the treatment. After treatment, these differences were eliminated in the Class II group; however, incisors were significantly protruded in both nonextraction groups. No other differences in profile or lip position were found between the extraction and nonextraction groups. The results of this study indicate that in successfully treated cases, whether by extraction or nonextraction, the same soft and hard tissue profile posttreatment end points were reached except for the incisor positioning, which is rather easier to anticipate than profile and soft tissue changes. The simple statement that extraction means a more retrusive or dished-in profile seems to be unacceptable. It seems that a more thorough assessment and investigation including pretreatment extent of crowding and factors related to anchorage, soft tissue thickness, and strain should be carried out.

Adolescent↗

PubMed2001

Serum-soluble human leucocyte antigen class I and class II concentrations as an alternative diagnostic test for determining immune indices required for normal pregnancies.

The levels of maternal immunostimulation (required throughout the gestation period) and immunosuppression (needed from the 8th week to labour), as assessed by the mixed lymphocyte reaction (MLR), have been successfully correlated with the outcome of pregnancy. Our laboratory has recently reported that serum-soluble human leucocyte antigen (HLA) class I and II concentrations can be predictive for successful pregnancy outcome. In fact, there is a direct correlation between soluble class II concentrations and maternal immunostimulation because, as expected, these serum HLA concentrations are augmented in the first and second trimester of pregnancy and remain stable thereafter. By the same token, serum HLA class I concentrations are low during the first trimester, correlating with the required absence of immunosuppression, whereas they increase in subsequent trimesters as suppression becomes desirable for counteracting the maternal stimulation, which may otherwise become dangerous to the fetus. In this study, we present biological and statistical evidence that both states of maternal immunostimulation and immunosuppression, reflected by serum soluble HLA class II and class I antigens, do correlate with results obtained by standard MLR and can be predictive of pregnancy failure. The establishment of statistically significant correlations renders the measurement of soluble HLA a reliable test for determining the immunological status of the gestating woman. The unambiguous advantage of such an approach is that soluble HLA testing will no longer require the 1 week delay necessary to obtain MLR results, a period occasionally crucial for applying treatment to women whose immunological indices call for immediate therapeutic intervention.

Adult↗

PubMed1997

Stability of empty and peptide-loaded class II major histocompatibility complex molecules at neutral and endosomal pH: comparison to class I proteins.

The structure and thermal stability of empty and peptide-filled forms of the murine class II major histocompatibility complex (MHC) molecule I-E(k) were studied at neutral and mildly acidic pH. The two forms have distinct circular dichroic spectra, suggesting that a conformational change may accompany peptide binding. Thermal stability profiles indicate that binding of peptide significantly increases the thermal stability of the empty heterodimers at both neutral and mildly acidic pH. Free energies calculated from these data provide a direct measure of this stabilization and show that the empty form of I-E(k) is significantly more stable than that of class I MHC proteins. Furthermore, for the two MHC class II proteins that were analyzed (I-E(k) and I-A(d)), thermal stability was not significantly altered by acidification. In contrast, of four class I MHC molecules studied, three have shown a significant loss in complex stability at low pH. The marked stability exhibited by their empty form, as well as their resistance to low pH, as observed in this study, correlate well with the ability of class II MHC molecules to traverse and bind peptides in acidic endosomal vesicles.

Amino Acid Sequence↗

PubMed1992

Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition.

The routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein (F) of measles virus (MV) to HLA class I and class II presentable peptides have been examined, using cloned cytotoxic T lymphocytes in functional assays. Presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines was achieved using live virus, ultraviolet light-inactivated virus, and purified MV-F delivered either as such or incorporated in immunostimulating complexes (MV-F-ISCOM). Only live virus and MV-F-ISCOM allow presentation by class I molecules, while all antigen preparations permit class II-restricted presentation. We observe presentation of MV-F from live virus and as MV-F-ISCOM by class II molecules in a fashion that is not perturbed by chloroquine. Our studies visualize novel presentation pathways of type I transmembrane proteins.

Animals↗

PubMed1993

The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC class II-restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production.

The immunological basis for atopy is currently ascribed to an inherent bias in the CD4+ T cell response to nonreplicating antigens presented at mucosal surfaces, resulting in dominance of the T helper 2 (Th2) interleukin 4 (IL-4)-producing phenotype, which favors IgE production. In contrast, the "normal" response to such antigens involves a predominance of interferon gamma (IFN-gamma)-producing Th1 clones. This difference has been suggested to be the result of active selection in atopics for Th2 (and hence against Th1) clones at the time of initial antigen presentation. In the study below, we demonstrate that the natural immune response to inhaled protein antigens, particularly in animals expressing the low immunoglobulin E (IgE) responder phenotype, includes a major histocompatibility complex (MHC) class I-restricted CD8+ T cell component, the appearance of which is associated with active suppression of IgE antibody production. Thus, continued exposure of rats to aerosolized ovalbumin (OVA) antigen elicits a transient IgE response, that is terminated by the onset of a state of apparent "tolerance" to further challenge, and this tolerant state is transferable to naive animals with CD8+ T cells. Kinetic studies on in vitro T cell reactivity in these aerosol-exposed rats demonstrated biphasic CD4+ Th2 responses which terminated, together with IgE antibody production, and coincident with the appearance of MHC class I-restricted OVA-specific IFN-gamma-producing CD8+ T cells. However, the latter were not autonomous in vitro and required a source of exogenous IL-2 for initial activation, which in CD(8+)-enriched splenocyte cultures could be provided by small numbers of contaminating OVA-specific CD4+ T cells. This represents the first formal evidence for the induction of an MHC class I-restricted T cell response to natural mucosal exposure to an inert protein antigen, and is consistent with a growing literature demonstrating sensitization of MHC class I-restricted CD8+ T cells by deliberate immunization with soluble proteins. We suggest that crossregulation of MHC class II-restricted CD4+ T cells via cytokine signals generated in parallel CD8+ T cell responses represents a covert and potentially important selection pressure that can shape the nature of host responses to nonreplicating antigens presented at mucosal surfaces.

Aerosols↗

PubMed2004

Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach.

MOTIVATION: Prediction of which peptides will bind a specific major histocompatibility complex (MHC) constitutes an important step in identifying potential T-cell epitopes suitable as vaccine candidates. MHC class II binding peptides have a broad length distribution complicating such predictions. Thus, identifying the correct alignment is a crucial part of identifying the core of an MHC class II binding motif. In this context, we wish to describe a novel Gibbs motif sampler method ideally suited for recognizing such weak sequence motifs. The method is based on the Gibbs sampling method, and it incorporates novel features optimized for the task of recognizing the binding motif of MHC classes I and II. The method locates the binding motif in a set of sequences and characterizes the motif in terms of a weight-matrix. Subsequently, the weight-matrix can be applied to identifying effectively potential MHC binding peptides and to guiding the process of rational vaccine design. RESULTS: We apply the motif sampler method to the complex problem of MHC class II binding. The input to the method is amino acid peptide sequences extracted from the public databases of SYFPEITHI and MHCPEP and known to bind to the MHC class II complex HLA-DR4(B1*0401). Prior identification of information-rich (anchor) positions in the binding motif is shown to improve the predictive performance of the Gibbs sampler. Similarly, a consensus solution obtained from an ensemble average over suboptimal solutions is shown to outperform the use of a single optimal solution. In a large-scale benchmark calculation, the performance is quantified using relative operating characteristics curve (ROC) plots and we make a detailed comparison of the performance with that of both the TEPITOPE method and a weight-matrix derived using the conventional alignment algorithm of ClustalW. The calculation demonstrates that the predictive performance of the Gibbs sampler is higher than that of ClustalW and in most cases also higher than that of the TEPITOPE method.

Algorithms↗

PubMed1999

The MHC class II ligand lymphocyte activation gene-3 is co-distributed with CD8 and CD3-TCR molecules after their engagement by mAb or peptide-MHC class I complexes.

Previous studies indicated that signaling through lymphocyte activation gene-3 (LAG-3), a MHC class II ligand, induced by multivalent anti-receptor antibodies led to unresponsiveness to TCR stimulation. Here, lateral distribution of the LAG-3 molecules and its topological relationship (mutual proximity) to the TCR, CD8, CD4, and MHC class I and II molecules were studied in the plasma membrane of activated human T cells in co-capping experiments and conventional fluorescence microscopy. Following TCR engagement by either TCR-specific mAb or MHC-peptide complex recognition in T-B cell conjugates, LAG-3 was found to be specifically associated with the CD3-TCR complex. Similarly, following CD8 engagement LAG-3 and CD8 were co-distributed on the cell surface while only a low percentage of CD4-capped cells displayed LAG-3 co-caps. In addition, LAG-3 was found to be associated with MHC class II (i.e. DR, DP and DQ) and partially with MHC class I molecules. The supramolecular assemblies described here between LAG-3, CD3, CD8 and MHC class II molecules may result from an organization in raft microdomains, a phenomenon known to regulate early events of T cell activation.

Animals↗

PubMed1998

HLA class I and class II antibodies: monitoring before and after kidney transplantation and their clinical relevance.

BACKGROUND: In search of an alternative screening technique, we compared complement-dependent cytotoxicity (CDC) with PRA-STAT, a commercially available enzyme-linked immunosorbent assay (ELISA). METHODS: A total of 188 pre- and posttransplant sera from 50 renal allograft recipients were tested with both methods. RESULTS: A significant correlation was found between both methods. Discrepant results could be explained by the fact that PRA-STAT detects both HLA class I and II antibodies (while CDC with peripheral blood lymphocytes as target cell detects mainly HLA class I reactivity), by the presence of IgM antibodies (which are not detected by the IgG-specific ELISA test), and by CDC "false-positive" results due to antibody rejection treatment. The clinical relevance of antibodies detected by PRA-STAT is suggested by the following. (a) In eight patients, donor-specific HLA antibodies detected by PRA-STAT (but not seen by CDC) resulted in severe rejection episodes, which led to graft loss in four cases. In all but one patient, antibodies were directed against class II or mixtures of class I and H antigens. Six patients with complications were shown to have developed de novo antibodies against DQ incompatibilities. (b) Half of the patients with a positive ELISA test at the moment of crossmatch experienced complications. Such patients are at a threefold higher risk of suffering from rejection episodes and/or graft loss than patients who are not sensitized (P<0.05, Fisher exact test). CONCLUSIONS: Because PRA-STAT is very reproducible, detects both HLA class I and II antibodies, and is not influenced by rejection therapy, we consider it an additional tool for pre- and posttransplant monitoring of kidney allograft recipients.

Antibodies↗

PubMed1998

HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia.

The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

Adult↗

PubMed1994

Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection.

Major histocompatibility complex (MHC) class I-deficient and MHC class II-deficient mice lack functional CD8 T cells and CD4 T cells, respectively. These mice were evaluated for infection following oral administration of 10(7) Cryptosporidium parvum oocysts. MHC class II-deficient (but not MHC class I-deficient) mice dosed with C. parvum oocysts at 3 to 5 days of age remained infected 8 weeks postexposure. MHC class II-deficient mice exposed to C. parvum oocysts at 5 to 6 weeks of age were significantly more susceptible to infection than control mice (P < 0.0001).

Animals↗

PubMed1995

Protective antitumor immunity induced by immunization with MHC class II gene-transfected tumor cells is unrelated to MHC class II expression.

A/JCr mice reject Sa1N fibrosarcoma cells genetically engineered to express major histocompatibility complex (MHC) class II molecules and are highly resistant to subsequent challenge with unmodified Sa1N cells. In this report we examine the mechanism by which this protective antitumor immunity is induced. We found that MHC class II antigen-positive tumor cells were no more effective than irradiated, MHC class II antigen-negative cells at inducing secondary protective immunity. Additionally, therapeutic immunization with MHC class II antigen-positive tumor cells had no effect on the growth of admixed Sa1N cells or preexisting Sa1N tumors. Based on these observations, we conclude that the MHC class II antigen-induced immune response is not related to Sa1N-specific antitumor immunity.

Animals↗

PubMed1996

Lupus nephritis in the absence of renal major histocompatibility complex class I and class II molecules.

MRL/Mp-lpr/lpr (MRL-lpr) mice develop an aggressive autoimmune disorder characterized by arthritis, vasculitis, and glomerulonephritis. Renal injury is associated with increased expression of major histocompatibility complex (MHC) molecules, as well as cytokines, adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1), and autoantibodies. By using either MHC Class I (MRL-lpr B2m-/-) or MHC Class II deficient (MRL-lpr Ab-/-) kidneys in a transplant model, we tested the role of renal expression of these molecules in the development of autoimmune renal injury. Kidneys from MRL-lpr B2m-/- or MRL-lpr Ab-/- mice as well as control wild-type mice transplanted into MRL-lpr wt/- recipients developed nephritis, CD4+ and CD8+ T cell infiltration, and heavy glomerular deposition of immunoglobulin. Spontaneously proliferating autoreactive T cells were found in wild-type MRL-lpr and MRL-lpr B2m-/- but not MRL-lpr Ab-/- mice. These results suggest that the absence of renal expression of either Class I or Class II molecules does not provide marked protection from autoimmune lupus nephritis and supports the possibility that protection from autoimmune disease in MRL-lpr Ab-1- mice is related to the loss of autoreactive MHC Class II-dependent CD4+ T cells.

Animals↗

PubMed1992

Inhibition of class I and class II MHC-restricted antigen presentation by cytotoxic T lymphocytes specific for an exogenous antigen.

Ag in the extracellular fluids can be internalized, processed, and presented in association with class I MHC molecules on specialized APC in normal spleen. We examine the fate of these APC after they present Ag to a CTL. When splenocytes present exogenous OVA to CTL, their ability to subsequently present native Ag in association with both class I and class II molecules is inhibited. CTL do not inhibit the ability of splenocytes to present processing independent peptides with class I or class II molecules. Inhibition of Ag presentation is only observed in the presence of the specific Ag recognized by the CTL. This inhibition is MHC-restricted. In the presence of specific Ag, CTL inhibit the ability of APC to present unrelated Ag. However, bystander APC are not affected by activated CTL. Taken together these results indicate that when APC present exogenous Ag to CTL, they are inhibited or killed. The CTL that mediates this activity has a conventional CD4-CD8+ phenotype and utilizes a TCR-alpha beta. The potential significance of these findings and their possible relationship to phenomena associated with Ts cells are discussed.

Animals↗

PubMed2005

[A study on the module using pendulum combined with straight wire appliance in Angle class II and skeletal class I malocclusion].

OBJECTIVE: To investigate morphologic changes of Angle class II and skeletal class I patients during pendulum and straight wire appliances treatment and to analyze the mechanism of this treatment protocol. METHODS: 10 patients with Angle class II and skeletal class I malocclusion were recruited. The lateral cephalometric radiographs were evaluated to determine if there were significant differences among pre-treatment (T1), after molar distalization (T2), and post-treatment (T3) variables including skeletal, dental and soft tissue relationships. RESULTS: Differences between the T1 and T2 means were significant for distal movement and distal angulation of the maxillary molars (P < 0.01), mesial angulation of the maxillary incisors (P < 0.05), mesial movement of the maxilla (P < 0.01) . There were no significant changes between T1 and T3 in respect saggital position and angulation of the maxillary molars (P > 0.05) . Only the mesial movement of lower first molars and upper and lower jaws were significant (P < 0.01) during the whole treatment. No upper second molar impaction was detected after treatment. CONCLUSION: The upper molars distalization could be achieved by pendulum appliance. The class I molar relationship could be obtained by the differential growth of jaws and the differential movement of upper and lower molars.

Cephalometry↗

PubMed1989

Modulation of major histocompatibility complex (MHC) class I genes in adenovirus 12 transformed cells: interferon-gamma increases class I expression by a mechanism that circumvents E1A induced-repression and tumor necrosis factor enhances the effect of interferon-gamma.

The protein products of the E1A gene of adenovirus type-12 (Ad12) block transcription of major histocompatibility (MHC) class I genes in both rodent and human transformed cells and interferon-gamma (IFN-gamma) is able to override this repression. Although IFN-gamma is known to stimulate class I transcription, we investigated whether its dominance over E1A repression could alternatively result from the ability of this cytokine to induce antiviral mechanisms. We show that this is not so, since the accumulation of Ad12 E1A mRNA and protein are unabated in the presence of IFN-gamma. Also, tumor necrosis factor (TNF) was shown to act synergistically with IFN-gamma to enhance class I antigen levels, although it had little effect alone. These results suggest that the normal pathway by which IFN-gamma acts to enhance the level of class I mRNAs, circumvents the block by which E1A represses class I transcription.

Adenovirus Early Proteins↗