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PubMed1988

The cataract Shionogi mouse, a sister strain of the non-obese diabetic mouse: similar class II but different class I gene products.

We have studied with a series of monoclonal antibodies and restriction fragment analysis the K, D, and class II region of the major histocompatibility complex of the non-obese diabetic mouse in comparison with its sister strains, the non-obese non-diabetic and cataract Shionogi mouse. (1) K region: Monoclonal antibody 31-3-4S (anti-Kd) reacted with splenocytes from non-obese diabetic mice while other anti-K (Kb, Kk, Kq) monoclonals did not react. Splenocytes from non-obese non-diabetic mice reacted with both anti-Kb and Kk monoclonals while splenocytes from cataract Shionogi mice reacted with anti-Kd and Kk monoclonals. Both sister strains, therefore, differ from the non-obese diabetic and other known mice strains by monoclonal analysis of H-2K. (2) D region: Splenocytes from both non-obese diabetic and non-obese non-diabetic mice reacted with monoclonal antibody 28-14-8S (anti-Db) while splenocytes from cataract Shionogi mice did not react with any anti-D monoclonal antibody tested. (3a) Class II region (non-obese diabetic and non-obese non-diabetic mice): Three of 11 monoclonal antibodies to class II molecules reacted with splenocytes of the non-obese diabetic mouse. The 3 reacting monoclonals have I-Ak primary specificities though additional anti-I-Ak monoclonal antibodies were negative. Among these monoclonals, 39B and 40A reacted with the non-obese diabetic mouse but not with the non-obese non-diabetic mouse, while 10-2-16 reacted with non-obese diabetic, non-obese non-diabetic and cataract Shionogi mice. Monoclonal MKD6 (anti-I-Ad) reacted with non-obese non-diabetic but not non-obese diabetic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Class I and class II major histocompatibility complex alleles are associated with faecal egg counts following natural, predominantly Ostertagia circumcincta infection.

During a previous investigation an association was found between major histocompatibility complex (MHC)-DRB1 alleles and faecal egg counts following natural infection predominantly involving Ostertagia circumcincta in a flock of Scottish Blackface sheep. To localise the disease-resistance locus we screened the same flock for an MHC class I microsatellite and a newly developed microsatellite for the DY locus located in the class IIb subregion. Some alleles at both additional loci were associated with resistance to infection. Least-squares analysis of variance indicated that in 6-month-old lambs, substitution of the most common alleles by the alleles associated with resistance would result in an 8- and a 218-fold reduction in faecal egg counts for MHC class I and DY, respectively. These results indicate that genes within the MHC genes play a large and significant role in the development of resistance to a widespread, important and natural parasite.

Alleles↗

PubMed1990

Differences in non-MHC restricted cytotoxic activities of human peripheral blood lymphocytes after transfusion with allogeneic leukocytes or platelets possessing class I and/or class II MHC molecules.

MHC-unrestricted cytotoxic activity of peripheral blood lymphocytes (PBL) from 4-6 healthy donors was investigated before and after transfusion with allogeneic leukocytes or platelets. Natural killer and lectin-dependent cellular cytotoxicity (LDCC) of PBL was tested against K562 and Raji target cells in a 4-h and 16-h 51Cr-release assay, respectively. After allotransfusion with leukocytes, we found increased cytotoxic activity of each donor's PBL against all the three targets on day 3 or 7. The highest non-specific cytotoxic activity was detected against the relatively NK resistant Raji target cells. The increase of cytotoxic activity was lowest against the LDCC target (PHA-treated Raji) cells. On the contrary, no changes in cytotoxic activity against any targets were observed after allotransfusion with platelets (possessing class I HLA antigens but no HLA class II molecules). Our results suggest that HLA class II molecules, presumably by inducing immune responses, are essential for activation/generation of non-specific killing of tumor targets after leukocyte transfusion. Thrombocytes, known to be less immunogenic than leukocytes, are not effective in in vivo enhancing of non-specific cytotoxicity. Cellular activation of PBL following leukocyte allotransfusion was confirmed by detection of elevated serum neopterin and beta-2-microglobulin levels on day 3. This was not the case after platelet allotransfusion. In addition, the expression of ICAM-1 antigen (as a molecule involved directly in MHC-unrestricted cytotoxicity) was also found to be increased in two donors' PBL on day 3 after leukocyte transfusion in contrast to transfusion with platelets.

Biopterins↗

PubMed1992

Hyoid bone position and orientation in Class I and Class III malocclusions.

Various studies have documented a variability of hyoid bone position in relation to changed mandibular position or head posture. The aim of this study was to investigate the hyoid bone position and inclination on the cephalometric radiographs of two groups of patients exhibiting Class I and Class III malocclusions. The radiographs were taken in both centric occlusion and wide-opened mandibular position, and 17 measurements were performed on both tracings. The findings reveal a statistically significant difference in the position and inclination of the hyoid bone in the two groups; Class III patients, especially the boys, show a more anterior position of the hyoid bone and also a reverse inclination. This might have an implication on the function of the suprahyoid and infrahyoid muscles and thus on the direction of mandibular growth.

Adolescent↗

PubMed2002

Precursors of functional MHC class I- or class II-restricted CD8alphaalpha(+) T cells are positively selected in the thymus by agonist self-peptides.

The origin and specificity of alphabeta TCR(+) T cells that express CD8alphaalpha have been controversial issues. Here we provide direct evidence that precursors of functional CD8alphaalpha T cells are positively selected in the thymus in the presence of agonist self-peptides. Like conventional positive selection, this agonist selection process requires functional TCR alpha-CPM, whereas it is independent of CD8beta expression. Furthermore, CD8alphaalpha expression on mature, agonist-selected T cells does not imply selection by MHC class I, and CD8alphaalpha(+) T cells can be either class I or class II restricted. Our data define a distinct agonist-dependent, positive selection process in the thymus, and they suggest a function for CD8alphaalpha distinct from the conventional TCR coreceptor function of CD8alphabeta or CD4.

Animals↗

PubMed2000

Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population.

HLA class I and class II allelic genotypes were determined in 371 unrelated individuals and 309 members of 81 families inhabiting the central Japan area. A total of 20 HLA-A alleles, 16 HLA-Cw alleles, 38 HLA-B alleles, 27 HLA-DRB1 alleles, 15 HLA-DQB1 alleles and 12 HLA-DPB1 alleles were detected. By the two-, three-, four-, five- and six-locus allelic association analyses extracted from the HLA-A to -DPB1 locus, 26 HLA-Cw-B haplotypes, 25 HLA-DRB1-DQB1 haplotypes, 42 HLA-Cw-B-DRB1 haplotypes, 37 HLA-Cw-B-DRB1-DQB1 haplotypes, 29 HLA-A-Cw-B-DRB1-DQB1 haplotypes and 21 HLA-A-Cw-B-DRB1-DQB1-DPB1 haplotypes with the frequencies of higher than 0.005 were recognized. Among 19 HLA-B alleles with the high allele frequencies (above 0.007), 9 HLA-B alleles, B*0702, B*1301, B*3701, B*3901, B*4006, B*4403, B*5201, B*5901 and B*6701 were found to be tightly associated with single HLA-Cw alleles. Most of HLA-DRB1 alleles showed strong associations with single HLA-DQB1 alleles, but DRB1*0802 and DRB1*1401 were associated with two different DQB1 alleles. Extended haplotypes carrying infrequent class I alleles with the allele frequencies of lower than 0.007 were defined by family studies. Gene frequencies and haplotypic associations within the entire HLA classical loci elucidated at the high resolution (four-digital) allelic level will provide useful information on anthropology, marrow donor registry, legal medicine and disease-association studies.

Family↗

PubMed2001

The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations.

The Caucasus and the Iberian peninsula have been connected from a linguistic (Basque and Kvartelian languages), toponimic and historic perspectives. They also represent places (e.g. Dmanisi in Georgia and Atapuerca in Northern Spain) where the oldest hominoid remains in Europe are being discovered and studied. These circumstances prompted us to study the genetic background of the Svans (living on the southern slopes of the Greater Caucasus in the Republic of Georgia) in comparison with Basques from the semi-isolated Arratia valley as well with other Northern Spanish and Western European populations. DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*1301-DQA1*0103-DQB1*0603 haplotypes were found in Svans at the highest frequency. The second most frequent three-locus haplotypes in this population were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1301-DQA1*0103-DQB1*0602. Furthermore, the following 5-locus extended haplotypes were not found in other populations: A3-B8-DRB1*11-DQA1*0501-DQB1*0301, A2-B8-DRB1*13-DQA1*0103-DQB1*0603, A2-B40-DRB1*14-DQA1*0104-DQB1*0501, A2-B51-DRB1*08-DQA1*0401-DQB1*0402, A3-B7-DRB1*03-DQA1*0501-DQB1*0201 and A24-B39-DRB1*08-DQA1*0401-DQB1*0402. Other haplotypes present in Svans were also frequently observed in Northern Spain and in other Western European countries. However, haplotypes reported as characteristic for Basques were not found in the Svans. A dendrogram using HLA class II alleles places the closest genetic distance observed between Svans and Czechs, whereas Slovenes and other Mediterranean populations (Jews, Hungarians, Frenchmen, Sardinians and Greeks) have the greatest genetic distance. When both HLA class I and class II alleles from 17 populations were compared, the smallest genetic distances were with Rumanians, Czechs and Armenians. Northern Spanish populations were placed closer to each other and clearly separated from Svans. In conclusion, the Svan population shows considerable polymorphism. These observations suggest a mixture of alleles in Svans from geographically distinct areas, and probably do not support a common ancestor for these Caucasian inhabitants and people from Northern Spain.

Alleles↗

PubMedDate not supplied

A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway.

Major histocompatibility complex (MHC) class I molecules export peptides to the cell surface for surveillance by cytotoxic T lymphocytes. Intracellular peptide binding is critical for the proper assembly and transport of class I molecules. This mechanism is impaired as a result of a non-functional peptide supply factor gene (PSF) in several human mutant cell lines with genomic lesions in the MHC. We have now identified PSF in the MHC class II region by deletion mapping in mutants and chromosome-walking. PSF is homologous to mammalian and bacterial ATP-dependent transport proteins, suggesting that it operates in the intracellular transport of peptides.

Amino Acid Sequence↗

PubMed2000

Tetanus toxin L chain is processed by major histocompatibility complex class I and class II pathways and recognized by CD8+ or CD4+ T lymphocytes.

Tetanus toxin (TeNT) is a heterodimeric protein antigen, whose light chain (L) is translocated in the cytosol of neuronal target cells specifically to cleave its substrates, vesicle-associated membrane protein-2 (VAMP-2, or synaptobrevin) or cellubrevin. We report that the L chain behaves as a nominal antigen recognized by specific T-cell clones upon either class I- or II-restricted presentation. Three types of responses are observed: (i) a TeNT- and L-specific CD8+ T-cell response, that can be inhibited in a dose-dependent manner by the proteasome inhibitor clasto-Lactacystin beta-lactone; (ii) a CD4+ T-cell response specific for L but not TeNT, with recognition of a determinant processed in a chloroquine-sensitive and brefeldin A-resistant compartment; (iii) a CD4+ T-cell response against both L and TeNT, with processing in a brefeldin A-sensitive compartment. The L chain processing was investigated in U937 cells by internalization and localization of L chain by separation of the cell content by differential centrifugation experiments. After incubation with TeNT or L chain in the presence of H chain, the L chain was predominantly distributed in the cytosolic fraction, whereas incubation with L alone led to localization in a lysosome/membrane fraction. The distribution of the TeNT L chain in both cytosolic and endocytic compartments of the antigen-presenting cell accounted for its processing by both class I and class II pathways. Furthermore, an epitope overlapping with the zinc-binding region was recognized by CD4+ and CD8+ T cells.

Antigen-Presenting Cells↗

PubMed2002

HLA-class 1 and class 2 antigens in Turkish patients with pemphigus.

BACKGROUND: Pemphigus is an autoimmune disease which is more frequently seen in certain ethnic groups such as Jews. It is thought that exogenous factors may induce pemphigus in genetically predisposed individuals. Recent reports on HLA antigens indicate an increased frequency of HLA-class II antigens particularly HLA-DR4 among Jewish patients. Herein we investigated the antigen frequencies of HLA-A, B, C, HLA-DR and DQ in Turkish patients with pemphigus. METHODS: HLA class I and II antigens were typed by microdroplet lymphocyte cytotoxicity test in 33 patients with pemphigus and 100 healthy individuals. RESULTS: HLA-B35, B44, CW4, DR4, DR14, DQ8 and DQ4 antigens were significantly high in the study group whereas HLA-DR11, DQ7 and DQ2 antigens were high among the controls. The most striking differences were observed in HLA class II antigens. HLA DR14-DQ8 and HLA B35-DR14 haplotypes were the most frequently observed ones in the study group. CONCLUSIONS: We postulate that HLA-B35, B44, CW4, DR4, DR14, DQ4 and DQ8 antigens may be responsible for susceptibility to pemphigus while HLA-DR11, DQ7 and DQ2 antigens may have a protective role in the Turkish population.

Adult↗

PubMed2004

[Control of vertical dimension in Root's technique. Part 1. Class I and Class III].

Does a technique using pre-adjusted brackets offer orthodontists advantages or stumbling blocks in their efforts to improve control of vertical dimension over the course of full-banded treatment? If pre-adjusted brackets are always helpful in hyper-divergent cases, how can orthodontists utilize them to the fullest extent? The author attempts to respond to these questions in a two-part article. The first section deals with the specific cephalometric and mechanical characteristics of hyper-divergent skeletal Class I and Class III cases by analyzing two clinical examples: the objective being to control the hyper-divergence. The second part is devoted to skeletal Class II malocclusions in which the hyper-divergence must be reduced in order to stimulate optimal anterior rotation of the mandible.

Cephalometry↗

PubMed1988

Qa-region class I gene expression: identification of a second class I gene, Q9, encoding a Qa-2 polypeptide.

A feature of the expression of the tissue-specific class I antigen Qa-2 is the quantitative variation among mouse strains. Recently, the class I gene Q7 has been shown to encode a protein product that is biochemically indistinguishable from the lymphocyte-bound Qa-2 molecule. Utilizing gene transfection, we have identified a second Qa-2 subregion class I gene (Q9), in H-2b mice, which encodes a polypeptide biochemically similar to the Q7 and the Qa-2 polypeptides. Furthermore, we have observed that cell lines transfected with the allelic forms of the Q7 gene from C57BL/10 (Qa-2hi) or BALB/C (Qa-2low) display quantitative differences in cell-surface expression. Based on these studies, we suggest that gene dosage and allele-specific variation in cell-surface expression contribute to the strain-specific variation in the levels of Qa-2 antigen expression.

Alleles↗

PubMed2000

Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam.

The influence of genes of the major histocompatibility complex (MHC) class II and class III loci on typhoid fever susceptibility was investigated. Individuals with blood culture-confirmed typhoid fever and control subjects from 2 distinct geographic locations in southern Vietnam were genotyped for HLA-DRB1 and HLA-DQB1 alleles, the gene that encodes tumor necrosis factor (TNF)-alpha (TNFA [-238] and TNFA [-308]), the gene that encodes lymphotoxin-alpha, and alleles of the TNF-alpha microsatellite. HLA-DRB1*0301/6/8, HLA-DQB1*0201-3, and TNFA*2 (-308) were associated with susceptibility to typhoid fever, whereas HLA-DRB1*04, HLA-DQB1*0401/2, and TNFA*1 (-308) were associated with disease resistance. The frequency of all possible haplotypes of the 3 individually associated loci were estimated and were found to be significantly different in typhoid case patients and control subjects (chi2=55.56, 32 df; P=.006). Haplotypes that were either protective (TNFA*1 [-308].DRB1*04) or predisposed individuals to typhoid fever (TNFA*2 [-308].DRB1*0301) were determined. This report identifies a genetic association in humans between typhoid fever and MHC class II and III genes.

Alleles↗

PubMed2003

Retroviral transfer of donor MHC class I or MHC class II genes into recipient bone marrow cells can induce operational tolerance to alloantigens in vivo.

Infusion of allogeneic, donor bone marrow (BM) can induce specific immunological unresponsiveness in vivo resulting in long-term acceptance of subsequent fully allogeneic, donor-type solid organ grafts, but this may be associated with graft-versus-host disease. We hypothesize that transfer of donor MHC gene(s) to recipient-type BM or hematopoietic stem cells would enable delivery of donor alloantigens to the recipient without the risk of graft-versus-host disease. This strategy could also potentially take advantage of linked suppression to induce specific unresponsiveness to additional alloantigens expressed by the solid organ graft. We found that infusion of 5 x 10(6) CBA (H-2(k)) recipient mouse BM cells transduced with a recombinant replication-defective retrovirus encoding either a single donor MHC class I or class II gene (H-2K(b) or H-2IA(b)) in combination with anti-CD4 monoclonal antibody resulted in long-term survival of C57BL/10 (H-2(b)) but not third-party NZW (H-2(z)) heart grafts. BM cells (3 x 10(3)) enriched for hematopoietic stem cells by sorting for c-Kit(+), lineage-negative cells, were able to induce long-term allograft survival in 50% of recipients after transduction with the vector encoding a single donor MHC class I gene. These results have important implications for future strategies to enhance clinical allograft survival by delivery of donor alloantigens.

3T3 Cells↗

PubMed2003

Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments.

Virions of filamentous bacteriophage fd are capable of displaying multiple copies of peptide epitopes and generating powerful immune responses to them. To investigate the antigen processing mechanisms in human B cell lines used as antigen presenting cells, the major coat protein (pVIII) in intact virions was fluorescently labeled, and its localization in various intracellular compartments was followed using confocal microscopy. We show that the virions were taken up and processed to yield peptides that reach both the major histocompatibility complex (MHC) class II compartment and the endoplasmic reticulum. Moreover, when exposed to bacteriophages displaying a cytotoxic T lymphocyte (CTL) epitope from the reverse transcriptase of human immunodeficiency virus type-1 (HIV-1), B cells were lysed by specific cytotoxic lymphocytes. This confirms that filamentous bacteriophage virions are capable of being taken up and processed efficiently by MHC class I and class II pathways, even in nonprofessional antigen presenting cells. These remarkable features explain, at least in part, the unexpected ability of virions displaying foreign T-cell epitopes to prime strong T-helper-dependent CTL responses. These findings have important implications for the development of peptide-based vaccines, using filamentous bacteriophage virions as scaffolds.

Antigen Presentation↗

PubMed1993

"Neutral allografts"--lack of allogeneic stimulation by cultured human cells expressing MHC class I and class II antigens.

Cultured human dermal fibroblasts, smooth muscle cells, epidermal cells and endothelial cells were tested for immunogenicity in an in vitro allostimulation assay. Gamma interferon was used to induce MHC class II expression, since these cells constitutively express class I but not class II antigens. In contrast to human dermal fibroblasts, smooth muscle cells and epidermal cells, endothelial cells, were able to stimulate a significant proliferative response in normal allogeneic lymphocytes. Since ICAM-1 was also expressed on these cells, this inability to initiate allostimulation was probably not due to the absence of adhesion molecules. Addition of exogenous cytokines such as IL-1, IL-2, and TNF did not restore T cell proliferation in the test system. Therefore the inability of dermal fibroblasts, smooth muscle cells, and epidermal cells to initiate significant allostimulation was also not due to lack of cytokine production. It appears that certain cells lack as-yet-undefined costimulatory factors required for their effective recognition as foreign. These results support the notion that cultured human fibroblasts, smooth muscle cells, and epidermal cells could serve as building blocks of engineered "neutral allografts" for use across MHC barriers.

Antigenic Modulation↗

PubMed2003

Infection of macaques with simian immunodeficiency virus induces a species-specific antibody response to major histocompatibility complex class I and class II molecules.

Envelopes of retroviruses, including human immunodeficiency virus and simian immunodeficiency virus (SIV), contain host cell proteins that potentially represent novel targets for vaccine development. We show here that sera from rhesus macaques recognized simian major histocompatibility complex (MHC) molecules in response to infection with SIV. Antibodies from these animals did not cross-react with human MHC antigens on mitogen-activated peripheral blood mononuclear cells. The development of antibodies to MHC class I alpha-chain did not correlate with anti-SIV envelope antibody responses, suggesting that these antibodies did not arise through molecular mimicry. In contrast to the species-specific response in infected animals, sera from animals vaccinated with inactivated human cell-grown SIV reacted to both human and rhesus MHC class I and class II molecules.

Animals↗

PubMed2004

Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis.

In order to analyze whether loci in the human leukocyte antigen (HLA) class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis (MS), we examined selected microsatellite markers in 177 Nordic sib-pair families, 222 British sib-pair families, 323 sporadic Norwegian MS patients and 386 Norwegian controls. All samples were, in addition, genotyped for the HLA-DR DQ haplotype, and the Norwegian case-control samples were also typed for HLA-A and -B loci. In the Norwegian sporadic MS patients association was seen with HLA-A, HLA-B, and with the D6S265 marker, located 100 kb centromeric to HLA-A. Associations with HLA-A and D6S265 loci were also suggested when restricting the analysis to HLA-DR15 haplotypes. In the sib-pair data a similar trend was seen with marker D6S265. Higher genotypic relative risk (GRR) was found for individuals who carry both HLA-DR15 and -A3 (GRR = 15), compared to those who carry only HLA-DR15 (GRR = 7), only HLA-A3 (GRR = 3) or none of these alleles (GRR = 1). The highest risk was conferred by a combination of HLA-DR15 and -A3 (odds ratio (OR) = 5.2). These results suggest that HLA-A or a gene in linkage disequilibrium with it may contribute to the HLA class II-associated genetic susceptibility to MS.

Case-Control Studies↗