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Results for “HLA-D Antigens”

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At least 19 recordsLinked to original sources
PubMed1976

HLA-D antigen of Japanese origin (LD-Wa) and its association with Vogt-Koyanagi-Harada syndrome.

One homozygous cell "Wa" for HLA-D alleles, associated with HLA-Bw22J (Japanese specific variant of HLA-Bw22), was found in a Japanese family. The HLA-D antigenic specificity defined by this cell has been tentatively named LD-Wa. Phenotype frequency of LD-Wa in the Japanese population was 0.16 (13/81). HLA-D typing for LD-Wa was performed in patients with the Vogt-Koyanagi-Harada syndrome (Harada's disease) with which Bw22J is strongly associated (15/35, 42.9%; corrected P less than 0.02). LD-Wa was presented in 22 of 33 patients (33.7%; P less than 0.0000003). The association of LD-Wa with Harada's disease was stronger than that of Bw22J, and this implies that there might be one of the disease susceptibility gene loci affecting the development of this disease more closely linked to an HLA-D gene locus than the HLA-B locus.

Epitopes↗
PubMed1977

Genetics of cell-mediated lympholysis in man.

Cell-mediated lympholysis (CML) was studied in a family containing two siblings in who genetic recombinaiton had occurred in the HLA comples. In one sibling, recombination occurred between the HLA-A locus and the HLA-B locus. In the second sibling recombination occurred between the HLA-B locus and the HLA-D locus. Strong CML activity was generated in mixed lymphocyte cultures (MLC) when stimulator and responder cells differed in HLA-A, B, and D antigens. MLC involving HLA-D differences alone did not generate CML. Weak, but definite CML activity was generated during MLC with cells differing at HLA-A and HLA-B but sharing HLA-D. HLA-B antigens were good targets for lysis in all combinations studied. HLA-A antigens were poor targets in some but not in all combinations. However, combinations where HLA-A antigens seemed to be good targets could have involved HLA-B differences due to polymorphism of HLA-B7 antigens each inherited from a different parent. HLA-D antigens did not serve as targets for lysis. In three cell experiments, excellent CML activity was generated when responder cells were stimulated by HLA-D antigens and by HLA-A and B antigens present on separate stimulator cells.

Adult↗
PubMed2025

Extensive Analysis of Genetic Diversity in HLA-DMA, HLA-DMB, HLA-DOA and HLA-DOB: Characterisation of 236 Novel Alleles.

HLA-DMA, -DMB, -DOA and -DOB are non-classical HLA Class II genes that play a crucial role in the selection of highly stable HLA Class II/peptide complexes on antigen-presenting cells. Although the genes were initially thought to have a limited diversity with less than 13 alleles per gene documented in the IPD-IMGT/HLA Database in 2022, recent studies suggest a potential impact of certain alleles on the outcome of hematopoietic cell transplantation. To gain a deeper understanding of allelic diversity, we sequenced HLA-DMA, -DMB, -DOA and -DOB of 1880 potential stem cell donors from Germany, Poland, Great Britain and Chile, achieving full-gene resolution. Remarkably, we identified 3968 previously undescribed sequences, including 28 distinct novel proteins. The observed allele frequencies were consistent across all studied populations with one dominating protein for each gene: HLA-DMA*01:01 (> 77%), HLA-DMB*01:01 (> 63%), HLA-DOA*01:01 (> 97%) and HLA-DOB*01:01 (> 77%). Notably, a much higher diversity was observed in full-genomic resolution. Finally, we submitted 51 distinct novel sequences for HLA-DMA, 58 for HLA-DMB, 80 for HLA-DOA and 47 for HLA-DOB to the IPD-IMGT/HLA Database. This comprehensive reference database update will not only simplify future genotyping of HLA-DMA, -DMB, -DOA and -DOB but will hopefully also enhance our understanding of the complex process of peptide selection and loading to the HLA Class II proteins.

Humans↗
PubMed2025

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↗
PubMed1976

Inhibition of the Fc receptor of human lymphoid cells by antisera-recognizing determinants of the hla system.

The inhibitory effect of HLA antisera on Fc receptors of human lymphoid cells was investigated. The ability of lymphoid cells to form rosettes (FcRFC) with antibody-coated sheep red blood cells and to function as effector cells (K cells) in antibody-dependent cell-mediated cytotoxicity were used as assay systems. We found that antisera recognizing determinants of the HLA-A, -B, and -C series had no effect on FcRFC, while a specific inhibitory effect was observed of antisera probably reacting with determinants identical to or closely associated with those of the HLA-D series. This inhibitory effect was retained in the F(ab')2 fragments. Specific inhibition of K cells was observed with all HLA antisera, but this effect was lost in the F(ab')2 fragments. We conclude that the Fc receptor of rosette-forming lymphocytes may be closely associated with products of the HLA-D region. This is analogous to the association between the Fc receptor and the Ia antigens on murine rosette-forming B lymphocytes.

Cross Reactions↗
PubMed1977

HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases.

Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation.

Adult↗
PubMed1976

Influence of HLA matching and blood-transfusion on outcome of 502 London Transplant Group renal-graft recipients.

The outcome of 502 cadaver kidney transplants has been followed for up to six years; these grafts were arranged through the Tissue Immunology Unit of the London Hospital Medical College, the coordinating centre of the London Transplant Group. An analysis of HLA (A and B) recepient-donor matching revealed, as in previous analyses, clear differences (now highly significant) between the best as compared with the lesser matched recipients. A quarter of the patients (group 4 and 3a) had a superior outcome 20-30% greater than poorly matched (2 or less group) which constituted 53% of individuals. The results in the 3b group (28% of patients) were intermediate 10-15% better than the "2 or less antigens in common" group. A small number of recipients mostly 4 or 3 matched who were retrospectively HLA-D matched showed an even better graft survival. The effect of blood-transfusion before transplantation was studied and found to improve the outlook especially in the best-matched groups. No difference was apparent between those receiving less or more than ten units except in a group of patients with cytotoxic antibodies and/or retransplants. This "immunocompetent-presensitised" group had the best outcome provided these recipients had few transfusions and were subsequently well matched. These findings emphasise the continued need for successful collaborative associations, so that improved matching can be achieved which if universally applied would ensure better graft survival for a large number of patients in renal failure.

Binding Sites, Antibody↗
PubMed1976

The genetics of cell-mediated lympholysis.

The role of HLA antigens in the generation of cytotoxic cells in CML has been investigated. Cytotoxic effector cells were generated in MLC among HLA-A or HLA-A and HLA-B disparate, HLA-D identical siblings, and among HLA-A and HLA-B disparate, MLC identical (%RR less than or equal to 2 3.6) unrelated individual. The data indicate that HLA-D differences and poliferative MLC responses as measured by 3H-thymidine incorporation are not requisite for the in vitro generation of cytotoxic cells and suggest the existence of a CML-S locus (loci) distinct from HLA-A, HLA-B and HLA-D. The degree of cytotoxicity generated in a proliferative versus a "nonproliferative" MLC was comparable. In addition, these studies demonstrate that antigens other than the currently definable HLA-A, HLA-B, HLA-C, and HLA-D can serve as target determinants in cell-mediated lympholysis.

Chromosome Mapping↗
PubMed1976

Joint report of the B lymphocyte specificities workshop of the France-one region.

The analysis of 182 selected anti-B cell sera on 102 cells allowed us to identifysseveral clusters of sera. They showed no correlation with HLA-A, B or C specificities but many associations with the HLA-D determinants. In 10 families, most of these sera segregated with HLA, and five recombinants showed a linkage with the BD or D end part of the MHC. The panel distribution and the family analysis indicated that at least one (the Ly-Li system) and probably two segregant series could exist close to the HLA-D locus.

B-Lymphocytes↗
PubMed1976

Typing for HLA-D determinants. comparison of typing results using homozygous stimulating cells and primed cultures.

Typing for HLA-D determinants, using primed lymphocyte typing (PLT), has been compared to the results obtained using conventional homozygous stimulating cell primary MLC tests. The HLA-Dwl, -Dw2 and -Dw3 specificities were studied. Preliminary results indicate that these two methods essentially type for the HLA-D determinants and that reproducible results can be obtained employing the PLT technique after 24 hours of incubation in the secondary cultures.

Epitopes↗
PubMed1976

[Determination by three technics of cellular immunology of the antigenic determinants of the Ly-Li system expressed on human B lymphocytes].

A clear correlation has been observed between the presence of the antigenic B cell system Ly-Li detected serologically, and 3 cellular immunology techniques: 1. MLR inhibition by anti-Li serum; 2. level of restimulation of anti-Ly-Li in vitro primed lymphocytes; 3. detection of HLA-D alleles by homozygous typing cells. These results suggest that the allelic products detected serologically may be identical to those detected by the first two techniques, namely MLR inhibition and in vitro primed lymphocyte typing, and possibly HLA-D typing using homozygous typing cells, although the correlation was found to be repeatedly less clear for the last technique.

B-Lymphocytes↗
PubMed1979

Polymorphism of the second component of human complement (C2). Observation of the rare phenotype (C2 2 (= C2 B) and data on the localization of the C2 locus in the HLA region.

The polymorphism of the second component of human complement was studied by means of isoelectric focusing in polyacrylamide gels with subsequent complement-dependent lysis of sensitized sheep erythrocytes in an agarose overlay containing C2-deficient or normal human serum. In a material of 289 unrelated individuals the following gene frequencies were observed: C21=0.965 and C22=0.035. The rare phenotype C2 2 (=C2 B) could be seen once in a child of a C2 1--2 heterozygous mother. The investigation of the C2/HLA relationship revealed a very close linkage: Among 62 informative meiotic divisions one recombination between HLA-B and C2 was found (i.e. 1.61%); in addition, C2(2) was significantly associated with HLA-B15 and -Cw3. In a family with an HLA-B/D(DR) crossover C2 segregated together with HLA-D(DR). This supports the assumption of a C2 structural locus outside HLA-B, probably near HLA-D(DR).

Alleles↗
PubMed1976

The impact of HLA-A, B or HLA-D identity on the MIF production in MLC.

The relative influence on MIF release in MLC of different parts of the HLA region was studied in 1) MLCs between cells from HLA-A and B identical (probably HLA-D unidentical) unrelated persons and 2) MLCs between cells from HLA-D identical, HLA-A and B unidentical unrelated persons. It was found that the HLA-D part of the region has the major effect on the MIF production. Studies of MIF activity in supernatants from mitomycin treated cultures lent some evidence to the hypothesis that there is an extreme linkage disequilibrium between the HLA-D alleles and hypothetical separate MIF alleles. Examination of families with crossover between the HLA-A, B and HLA-D part of the region is required for confirmation of these findings.

Epitopes↗
PubMed1978

Successful transplantation of marrow from an HLA-A, -B, -D mismatched heterozygous sibling donor into an HLA-D-homozygous patient with aplastic anemia.

A patient with aplastic anemia who was found to be homozygous for an HLA-D determinant shared by her unrelated parents achieved sustained engraftment and full restoration of hematopoietic and lymphoid function following a transplant from an HLA-A and -B nonidentical, ABO incompatible sibling who was heterozygous for the shared HLA-D specificity. Transplantation was complicated by transient graft-versus-host disease of moderate severity, which resolved completely following treatment with antithymocyte globulin and prednisone. The case indicates that patients found to be HLA-D-homozygous may be successfully transplanted from HLA-D-heterozygous sibling donors despite HLA-A and HLA-B incompatibilities, and thus further demonstrates the importance of the HLA-D region as a marker of donor-host histocompatibility.

Anemia, Aplastic↗