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At least 19 recordsLinked to original sources

HLA-DP antigen and Takayasu arteritis.

Sixty-four patients with Takayasu arteritis and 317 healthy individuals in the Japanese population were examined for HLA-A, -B and -C alleles by serological typing and for HLA-DR, DQ and DP alleles by DNA typing using PCR/SSOP analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601 and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the combination or haplotype of HLA-Bw52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 -DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another combination or haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. Because this is the first evidence for the association between an HLA-DP allele and Takayasu arteritis, we examined the nucleotide sequences of the DPB1*0901 allele from a patient and her healthy relatives and found no difference. The disease is therefore not caused by a mutated DPB1 gene.

Alleles↗

[Expression of HLA-DP antigens on normal and leukemic blood cells].

HLA-DP allodeterminant elicit weak cellular and humoral immune responses. This study was undertaken to find out if the low immunogenicity of HLA-DP could be accounted for by a low level of expression on peripheral blood mononuclear cells. Double staining experiments and flow cytometry were performed in 28 healthy individuals, HLA-DP was found to be as expressed as DR and DQ on B lymphocytes. Furthermore, a DP+/DR- lymphocyte sub-population was identified and characterized as freshly activated T lymphocytes.

Adult↗

[Use of monoclonal antibodies against human HLA II antigens for the detection of bovine B lymphocytes and macrophages].

The crossreactivity of mouse monoclonal antibodies (MoAbs) (Tab. I) prepared against human HLA-DR and HLA-DP antigens was studied in various bovine cells: lymphocytes from lymph nodes and peripheral blood, adherent (B) and nonadherent (T) lymphocytes, monocytes, granulocytes and platelets. In the immunofluorescence test, MoAbs Bra13, Bra14, Bra20, Bra22, Bra30, Bra70, HL-38 reacted with bovine B lymphocytes and monocytes, but not with other tested cells (Tab. III, IV). These antibodies, except Bra22, were positive with B lymphocytes in the complement dependent cytotoxic test (Tab. II). The similarity of the bovine antigens and HLA-DR antigens determined by used MoAbs was also proved by immunoblotting. Monoclonal antibodies Bra38 and BraFB6 did not react with the bovine cells and separated antigens. The epitope (HLA-DR) recognized by the antibody Bra38 is probably absent in cattle. The presence of HLA-DP analogue determined by the antibody BraFB6 has not been confirmed. The crossreactive MoAbs could be used for the detection of B lymphocytes and macrophages in veterinary immunology.

Animals↗

Influence of HLA-DR2, HLA-DPw4, and T cell receptor alpha chain genes on the susceptibility to multiple sclerosis.

In view of our recent report that T cell receptor (TCR) alpha chain restriction fragment length polymorphism (RFLP) is associated with multiple sclerosis (MS), we have assessed the possibility that HLA-DR2, HLA-DPw4, and TCR alpha chain RFLPs may interact to increase the risk of developing MS. Detection of TCR alpha chain polymorphisms, and HLA-DR and -DP typing were carried out by RFLP analysis on MS patients and healthy controls from the Melbourne metropolitan area. Interaction effects among these loci in producing susceptibility to MS were assessed by hierarchial log-linear analysis. Although HLA-DR2 was significantly associated with MS (chi 2 = 9.30, P = 0.002), no interactive effect between MS and HLA-DPw4 was observed. Significant interactions were observed with MS and both C alpha and V alpha, with the strongest effect seen with C alpha (chi 2 = 21.30, P less than 0.001). The combination of DR2/C alpha imparted a relative risk of 47. However, when the data were analysed for four and three way interactions, no significant effects were seen with MS, DR2, DPw4, V alpha, and C alpha, implying that the combined presence of these polymorphic markers is not essential for increasing susceptibility to MS.

Biomarkers↗

DP epitope mapping by using T-cell clones.

To determine whether a correlation exists between the genomic HLA class II DP DNA polymorphism and cell surface expression and to detect the DP epitopes responsible for alloreactivity, anti-DP T-cell clones were generated against new PLT blank RFLP DPa and DPb-defined specificities. The clones were tested on the 10th IHWS B-LCLs and on local panel cells. Oligotyping of the tested cells made it possible to (a) correlate the DPa specificity with the DPB1*0402 specificity and (b) split DPb into DPB1*1001 and DPB1*1401. By comparing DNA sequences of the second exon to panel reactivity, the epitopes responsible for DPB1*1001 and 1401 were defined and attributed to beta-chain residues contributing to peptide selection inside the HLA groove. However, DNA sequences could not explain anti-DPa allospecificity, indicating that another structure not yet definable may be involved.

Amino Acid Sequence↗

Polymerase chain reaction--single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple, economical, and rapid method for histocompatibility testing.

A new technical trial was carried out to detect polymorphism in HLA-DP genes, based on the diversity in electrophoretic mobility of single-stranded DNA (single-strand conformation polymorphism, SSCP). Genomic DNAs from 31 cell lines homozygous for 2 and 14 different DPA1 and DPB1 alleles, respectively, and from peripheral blood cells of a normal individual homozygous for another DPB1 allele were subjected to polymerase chain reaction (PCR) to amplify the polymorphic exon 2 of DPA1 or DPB1 genes. The PCR samples were denatured by heating in the presence of formamide to obtain single-stranded DNA, electrophoresed in a neutral polyacrylamide gel, and visualized by silver staining. Allelic differences were detected by the distinctive electrophoretic pattern of each single strand, depending on the sequence-specific conformation. Fifteen DPB1 alleles showed 11 distinct electrophoretic patterns, leaving four allelic combinations not distinguished. These four allelic combinations could be further distinguished by using another couple of primers in PCR, with which a part of the exon was amplified, and by subsequent SSCP analysis. The use of four pairs of primers in PCR allowed for discrimination of all the 15 DPB1 alleles tested. Two allelic differences in exon 2 of DPA1 gene could be clearly demonstrated. In addition, putative new alleles of DPA1 and DPB1 genes were detected by SSCP analyses. The PCR-SSCP analysis is simple and rapid, requires neither radioactive materials nor restriction enzymes, and is expected to be a useful tool for investigating the fine HLA-matching required for clinical transplantation of organs.

Alleles↗

V delta 1+ subset of human gamma delta T cells responds to ligands expressed by EBV-infected Burkitt lymphoma cells and transformed B lymphocytes.

Human gamma delta T cells of peripheral blood can be divided in two groups in terms of their TCR as well as their behavior upon in vitro stimulation. The major subset expresses the TCR V-segments V gamma 9 and V delta 2 and proliferates in response to ligands revealed by various microorganisms, and the cell line Daudi in addition. The minor group is less homogenous on the gamma-chain but is almost completely identified by mAb against the V delta 1 segment; there is no ligand known to promote growth of these cells. Here we demonstrate that gamma delta T cells out of this subgroup are strongly stimulated in vitro by cells from several Burkitt's lymphoma cell lines. EBV infection of the Burkitt's lymphoma cell lines enhanced the stimulatory ability towards the T cells. Although EBV infection influenced the expression of a variety of cell surface molecules including ICAM-1 and LFA-3, no correlation to the gamma delta T cell-stimulating capacity became apparent. We conclude that Burkitt's lymphoma cells and transformed B cells express ligands of cellular origin for a hitherto poorly characterized subgroup of human gamma delta T cells.

B-Lymphocytes↗

HLA-DP region gene polymorphism in primary IgA nephropathy: no association.

Many features suggest that a genetically mediated abnormality of the IgA immune response is central in the pathogenesis of IgA nephropathy (IgAN). Candidate disease susceptibility genes include those encoding the MHC class II antigens, HLA-DR, -DQ, and -DP, and we have recently described an HLA-DQB1 association in IgAN. Polymorphisms of the HLA-DP region loci have been shown to associate with autoimmune diseases which share immunological features with IgAN; coeliac disease (CD) and dermatitis herpetiformis (DH). We have therefore examined restriction fragment length polymorphisms (RFLPs) of the DP alpha and DP beta chain genes (DPA1 and DPB1 respectively) in IgAN, and have studied three caucasoid populations (North, Mid, Southern Europe) to determine whether ethnic variation in genetic susceptibility exists. DNA was extracted from blood (IgAN, UK n = 89, Italy n = 75, Finland n = 49; Controls, UK n = 99, Italy n = 54, Finland n = 45), and studied by Southern blot hybridization techniques using the restriction enzymes BgI II and Msp I and cDNA 32P-labelled DPA1 and DPB1 probes respectively. The frequency distribution of the DPA1 and DPB1 fragments was similar between the three caucasoid IgAN patient groups compared to their respective controls. There was no association of DPA1 or DPB1 RFLPs with clinical features. These results suggest that HLA-DP region genes are not important in conferring disease susceptibility to IgAN and do not influence clinical disease expression. Moreover, different immunogenetic mechanisms operate in IgAN, CD, and DH.

Glomerulonephritis, IGA↗

HLA-B Serine 116 Confers Protection Against Severe COVID-19 in a Cohort From Rio de Janeiro, Brazil.

COVID-19 is a respiratory disease caused by SARS-CoV-2, in which severe outcomes are primarily driven by an exacerbated immune response. The HLA region has been extensively investigated in COVID-19 due to its central role in the immune response, although genetic associations vary across populations. Here, the association of HLA genetic variability with COVID-19 severe respiratory outcomes was investigated in an admixed population from Rio de Janeiro, Brazil. Results of a comparative study between mild and severe COVID-19 cases involving 306 individuals have suggested risk associations with severe COVID-19 for the HLA-DPB1*13:01 allele (OR = 3.42, 95% CI = 1.05-11.16, p = 0.041) and the HLA-B*39 allele group (OR = 3.26, 95% CI = 1.16-9.13, p = 0.024), although statistical significance was lost after FDR adjustment for multiple comparisons (adjusted p > 0.05). Amino acid analyses showed that a serine at position 116 of HLA-B conferred protection against severe COVID-19 (OR = 0.4774, 95% CI = 0.28-0.81, p = 0.006, adjusted p = 0.031). In silico analysis using the NetMHCpan tool predicted that this residue, located in the HLA-B peptide-binding groove, has enhanced binding affinity to immunodominant SARS-CoV-2 epitopes, suggesting a functional mechanism underlying the observed protection. The association of single nucleotide variants at the HLA region was also investigated, and no statistically significant association was found. Results obtained in the present study underscore the importance of HLA in COVID-19 severity, likely mediated by its influence on viral peptide presentation, and advance our understanding of the genetic underpinnings of severe disease in admixed populations.

Humans↗

Involvement of major histocompatibility complex class II antigen in Epstein-Barr virus-mediated B cell proliferation.

Five MHC class II monoclonal antibodies costimulated proliferation of cord blood leukocytes with Epstein-Barr virus. These agonistic antibodies were of different isotypes, but all of them were either specific for or cross-reacting with HLA-DR. The other MHC class II antibodies, including three that were specific for HLA-DQ and one that was specific for HLA-DP and also those that were specific for MHC class I or leukocyte common antigen, were not costimulatory. The agonistic effect of different MHC class II antibodies was additive, such that costimulation by different antibodies combined significantly exceeded that achieved by either of these antibodies alone. Spent culture media of B cell lines also costimulated B cell proliferation with the virus. Although MHC class II antibodies augmented the effects of suboptimal concentration of the conditioned media, their combined effects did not exceed the maximum costimulation achieved by either the antibodies or the spent culture media alone. These results raised the possibility that MHC class II antigen may contain distinct functional domains involved in the regulation of B cell progression.

Antibodies, Monoclonal↗

Th1 lymphokine production profiles of nickel-specific CD4+T-lymphocyte clones from nickel contact allergic and non-allergic individuals.

Panels of nickel-specific T-lymphocyte clones (TLC) were prepared from nickel-allergic and non-allergic donors. TLC from both panels showed similar levels of expression of TCR alpha/beta, CD4, CD2, CD25, and CD29 and recognized nickel in association with class II HLA molecules with restriction determinants in HLA-DR, HLA-DP, and HLA-DQ. The lymphokine secretion was analyzed in TLC from both panels upon antigen-specific or non-specific stimulation and was compared with the secretion profiles of representants of pre-established human atopen-specific Th1 and Th2 cells. Nickel-specific TLC from both panels showed a lymphokine secretion pattern similar to the atopen-specific Th1 cells, although there was some variation from clone to clone. Most TLC secreted substantial amounts of IFN-gamma, IL-2, TNF-alpha, and GM-CSF, but little or no IL-4 and IL-5. The variation observed mainly concerned IL-2 secretion that could be low or absent in some of the TLC. The general secretion pattern did not change upon different modes of stimulation, including activation via CD3, CD2, or CD28. Because nickel-specific TLC from allergic and non-allergic individuals show a similar Th1 secretion pattern, the present results give no evidence that aberrant lymphokine secretion by CD4+T cells determines the contact allergic state, as was found for atopic allergy in a previous study.

CD4-Positive T-Lymphocytes↗

Differential Alloreactivity: Lessons Learned From a Singular HLA Locus.

Alloreactivity entails the recognition of cells and tissues from one individual as foreign by T cells and other immune effectors from another individual. Alloreactive immune responses play an important role in various clinical contexts, in particular in transplantation. Major drivers of these responses are the highly immunogenic, non-self HLA molecules. However, the immunogenicity of these allogeneic HLA molecules has been observed to vary according to certain immunobiological and immunogenetic parameters, leading to the concept of differential alloreactivity. Recent progress in unveiling the underpinnings of this phenomenon has been made for the frequently mismatched HLA-DP allotypes, whose singular genomic, structural and population genetics characteristics offer an ideal scenario for these investigations. Studies in the HLA-DP context have highlighted the immunopeptidome overlap between self and non-self HLA allotypes, as well as its editing by non-classical class II chaperones HLA-DM and HLA-DO, as a main determinant of their immunogenicity likely via indirect effects of thymic education. Recent evidence suggests that these observations could also be extended to alloresponses directed against HLA molecules encoded by other loci. How these functional characteristics of HLA molecules shape allorecognition by T-cell subsets, and how they translate into different clinical consequences in the context of transplantation will be the subject of the present review.

Humans↗

MHC class II determinants on peripheral blood monocytes from newly diagnosed IDDM patients.

The expression of MHC class II determinants (HLA-DR, HLA-DP and Ia7) on peripheral blood monocytes (OKM1+ cells) was studied in 20 children with newly diagnosed IDDM. Monocytes of 10 children with IDDM and familial predisposition showed a statistically significant increase of HLA-DR expression when compared to control group (10 healthy children). There were no significant differences concerning Ia7 expression. HLA-DP expression was similar in all studied groups.

Adolescent↗

Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue.

Expression of proteins associated with immune function was investigated immunohistochemically in postmortem brain and spinal cord of patients with amyotrophic lateral sclerosis (ALS). Reactive microglia/macrophages displaying high levels of leukocyte common antigen (LCA), the immunoglobulin receptor Fc gamma R1, lymphocyte function associated molecule-1 (LFA-1), the complement receptors CR3 and CR4, the class II major histocompatibility complex molecules HLA-DR, HLA-DP and HLA-DQ and common determinants of the class I HLA-A,B,C complex were abundant in affected areas in ALS. These areas included the primary motor cortex, motor nuclei of the brain stem, the anterior horn of the spinal cord, and the full extent of the corticospinal tract. A significant number of T lymphocytes of the helper/inducer (CD4+) and cytotoxic/suppressor (CD8+) subtypes were observed marginating along the walls of capillaries and venules and extending into the parenchyma of affected areas. Clusters of complement activated oligodendroglia as well as degenerating neurites positive for C3d and C4d were frequently detected in ALS-affected areas. These data provide evidence of immune-effector changes in ALS. They are consistent with an autoimmune or slow virus theory of the disorder, but may reflect only secondary changes.

Amyotrophic Lateral Sclerosis↗