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Results for “Histocompatibility Antigens”

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PubMed1991

Minor histocompatibility antigens.

Histocompatibility antigens have been studied for over 50 years because they form a major obstacle to clinical transplantation. Human minor histocompatibility antigens remain ill-defined, but minor histocompatibility loci have been mapped on nearly every mouse chromosome. Recent molecular definition of several transplantation antigens suggests that they are by-products of an immune system poised to present viral antigens, and a mutation in any gene may give rise to a new minor histocompatibility antigen.

Amino Acid Sequence↗
PubMed2007

Duffy and Kidd blood group antigens: minor histocompatibility antigens involved in renal allograft rejection?

BACKGROUND: Minor histocompatibility antigens have been poorly defined. Whether Duffy (FY) and Kidd (JK), polymorphic and immunogenic blood group antigens, widely distributed in human organs, expressed and functional in the kidney, could function as minor histocompatibility antigens and be implicated in renal allograft rejection was questioned. STUDY DESIGN AND METHODS: A retrospective, homogeneous, single-center cohort of 370 renal transplants was analyzed. In all donor/recipient pairs, FY and JK polymorphisms were identified by real-time polymerase chain reaction. In all donor/recipient pairs the matching (m) or mismatching (mm) status was defined for both systems. All biopsies were reviewed, and historical screening results for FY and JK alloantibodies and graft survival were retrospectively analyzed. RESULTS: Although graft survival was not different between the groups, it was observed that FY mm grafts had significantly more chronic lesions compared to FY m grafts. HLA-DR11 was more frequent in both recipients (p = 0.0081) and donors (p = 0.0104) of FY mm couples without chronic allograft nephropathy, suggesting a protective effect for this molecule. JK mm grafts had more interstitial inflammation than JK m grafts (p = 0.0369). CONCLUSION: This renal model unmasks for the first time the role of FY and-to a lesser extent-JK antigens as minor histocompatibility antigens and suggests their potential role for other clinical transplant settings.

Adolescent↗
PubMed1981

Transplantation in miniature swine. IX. Swine histocompatibility antigens: isolation and purification of papain-solubilized SLA antigens.

Histocompatibility antigens have been purified by papain treatment of crude cellular membranes obtained from spleen and mesenteric lymph nodes of individual miniature swine that are homozygous at the major histocompatibility complex. The purification protocol included ultracentrifugation, gel filtration, ion-exchange chromatography, and in some instances preparative isoelectric focusing. This procedure was applied to the preparation of sLA antigens from the 3 haplotypes available in our partially inbred miniature swine herd. The purity of the SLAdd molecules was evidenced by: 1) a single activity peak of approximately 50,000 daltons on gel-permeation chromatography; 2) the antigen elution as a symmetrical peak from ion-exchange resins and from isoelectric focusing columns; 3) the presence of 2 predominant polypeptide chains on SDS-PAGE at apparent m.w. 43,000 and 13,000 daltons; and 4) specific immunoprecipitations by alloantisera and by anti-beta 1 microglobulin antisera. The antigenic activity of SLA products was analyzed by inhibition of complement-mediated cytotoxicity and by removal on anti-beta 2-microglobulin affinity columns. Heavy and light chains were separated by gel-filtration on Sephacryl S-200 in 6 molar guanidine. These SLA products, which have thus been shown to be pure by a variety of criteria, are now readily available for structural analysis and for analysis of biologic activity.

Animals↗
PubMed1986

Immunodominance in the T cell response to multiple non-H-2 histocompatibility antigens. III. Single histocompatibility antigens dominate the male antigen.

Immunization of mice with multiple non-H-2 histocompatibility antigens results in the generation of cytolytic T lymphocytes that are specific for a limited number of immunodominant antigens. The experiments presented in this communication were designed to reveal immunodominance in pairwise combinations of autosomal and sex-linked non-H-2 histocompatibility (H) antigens. Priming and boosting responders with the male antigen, H-Y, paired with the H-4.2, H-7.1, or H-3.1 antigens, resulted in the generation of cytolytic T cells specific for the autosomal H antigens but not the H-Y antigen. Furthermore, co-immunization and boosting of C57BL/6 female responder spleen cells with BALB.B male cells resulted in the generation of cytolytic T cells specific for the BALB.B immunodominant antigens but not H-Y. No dominance was observed in H-4-plus H-7-incompatible combinations. Co-immunization of three different H-3 congenic strains with H-3.1 plus H-Y demonstrated that an efficient anti-H-3.1 T cell response is required for observing H-3.1 immunodominance over H-Y. Co-expression of H-3.1 and H-Y on the same priming and boosting cells was required for immunodominance. In fact, immunization with H-3.1 and H-Y presented on different cells resulted in normal generation of H-Y-specific cytolytic T cells, but no generation of H-3.1-specific cytolytic T cells resulted unless H-Y-specific cells were stimulated in the mixed lymphocyte cultures. These observations suggest that in vitro T cell responses to paired, non-H-2 H antigens may be independent, competitive, or synergistic, depending on the identity of the antigens and the priming and boosting conditions.

Animals↗
PubMed1987

Psoriatic arthritis: clinical subgroups and histocompatibility antigens.

Histocompatibility antigens were determined in 60 patients with psoriatic arthritis. The patients were divided into clinical subgroups according to axial or peripheral joint involvement, disease severity based on number of peripheral joints involved, and the presence or absence of bone erosions. The total group showed a significant increase in frequency of HLA-A1, B17, B27, and DR7 when compared with a control population. The subgroup with spondylitis had a significant increase in frequency of HLA-B27 when compared with patients with peripheral arthritis (p less than 0.001). The subgroup with peripheral arthritis alone had a higher frequency of HLA-DR7 than the control group (p less than 0.001). There were also significant associations between HLA-DR7 and chronic severe disease (p less than 0.001) and between HLA-DR4 and the presence of erosions (p less than 0.05).

Arthritis↗
PubMedDate not supplied

The undefined relationship between tumor antigens and histocompatibility antigens on cancer cells.

The data pertaining to the possible relationship between histocompatibility antigens (HA) and tumor-specific transplantation or tumor surface antigen (TSTA or TSA) are reviewed. The HA profiles of certain experimental and human neoplasms have been found to be altered either from the quantitative (increased expression of some antigenic specificities and decreased expression or even lack of other HA) or qualitative point of view (appearance of alien, genetically inappropriate HA). The authors entertain the possibility that the persence of TSTA or TSA on cancer cells may be linked to alterations of the HA profile. Evidence in favour of the idea that tumor antigens may actually to alien MHC products, alien minor HA or modified HA, is reviewed. Findings on structural relationships between TSA and beta2-microglobulin are also summarized. In the authors' opinion, no definitive conclusions can be reached at the present time on the relationship between TSTA or TSA and HA of cancer cells.

Animals↗
PubMed1976

Ability of delayed-type hypersensitivity reactions to distinguish tumor-associated antigens and histocompatibility antigens in soluble extracts from murine fibrosarcomas.

The footpad swelling (FPS) test for delayed-type hypersensitivity in the mouse was evaluated for its ability to measure both tumor-associated antigens (TAA) and histocompatibility (H) antigens solubilized from methylcholanthrene (MCA) induced fibrosarcomas of C57B1/6 (B6) mice. Tests for TAA were performed in mice immune to syngeneic tumors while H-antigens were assayed in mice immunized with skin allografts. FPS was most intense in B6 mice challenged with TAA from the immunizing B6 tumor, but also occurred in response to cross-reactive TAA solubilized from another B6 fibrosarcoma. Tests for tumor-associated H-antigens in allograft immune mice were strongly positive in response to donor/recipient H-antigen differences and proved sensitive to shared third-party H-antigen differences. Comparison of soluble antigens from the same tumor maintained in vitro and in vivo revealed that, while both TAA and H-antigens could be detected in preparations from the in vivo tumor line, only TAA and not H-antigens could be detected by RPS in extracts prepared from the in vitro tumor line. These experiments have demonstrated that the mouse FPS test can distinguish both TAA and H-antigen specificities persent in the same complex mixture of tumor-cell antigens.

Animals↗
PubMed1981

Differential effect of interferon on the expression of tumor-associated antigens and histocompatibility antigens on human melanoma cells: relationship to susceptibility to immune lysis mediated by monoclonal antibodies.

Incubation of cultured human melanoma cells with human leukocyte interferon did not change the expression of melanoma-associated antigens (MAA) recognized by monoclonal antibodies and of Ia-like antigens but significantly increased the expression of HLA-A,B antigens and of beta 2-microglobulin (beta 2-mu). The effect is dependent on the dose of interferon and on the incubation time. Interferon-treated melanoma cells showed an increased susceptibility to lysis mediated by monoclonal antibodies to HLA-A,B antigens and to human beta 2-mu; on the other hand, interferon-treated melanoma cells did not change in their susceptibility to murine natural killer (NK) cell lysis and to immune lysis mediated by monoclonal antibodies to MAA and to Ia-like antigens, and they displayed a reduced susceptibility to human NK cell lysis. Therefore, the increased susceptibility of interferon-treated melanoma cells to lysis mediated by anti HLA-A,B and anti beta 2-mu monoclonal antibodies is likely to reflect the increase in cell surface expression of the corresponding antigens.

Animals↗
PubMed1996

Histocompatibility antigens in patients with hepatocellular carcinoma.

The distribution of class I (A, B, C) and class II (DR antigens) histocompatibility antigens (HLA) was examined in 82 patients with hepatocellular carcinoma (HCC) and in 147 patients with chronic liver disease as controls. The diagnosis of HCC was confirmed by histological examination of liver tissue. HLA-B15 antigen was found more frequently in the subgroup of HCC patients who were positive for HBsAG (13/36, 36.1%) compared to the control group (8/147; 5.4%) [p < 0.001, Pc < 0.05, RR = 9.8] and a HBsAg positive control subgroup (1/25, 4%) [p < 0.001, Pc < 0.05, RR = 13.6]. No other statistically significant difference was found for any of the HLA antigens examined either in HCC patients as a whole group or in the subgroups according to sex, course of illness, AFP status, alcohol consumption, liver cirrhosis or blood groups. These data are further evidence that there may be a link between hepatitis B viral (HBV) infection and HLA antigens. The association of HLA-B15 antigen and HbsAg supports the idea of some genetic control of HBV infection in the patients with HCC.

Adult↗
PubMedDate not supplied

[Relationship between tumor antigens and histocompatibility antigens at the cell membrane].

The authors outline schematically the major histocompatibility complex as well as the relationship between tumor neo-antigen and pre-existing antigens at the cell surface. They note that these two antigenic systems are not independent and in particular, the major histocompatibility system (H-2) co-segregates with the tumour antigens. Considering the complexity of the H=2 system (a H-2 allele does not correspond to any single transplantation antigen but to a combination of several antigens units simultaneously present), the authors recall Boyse's hypothesis, revised by Haywood and Mc Khann, which propose that tumour antigens are a rearrangement of H-2 substructures. Moreover, it is possible that the relationship between H-2 and resistance to cancer may be attributed directly to the action of genes controlling the immune response (Ir region) which could also intervene in recognition of these tumour antigens. Finally, recent results obtained seem to show that some tumour antigens cross-react with H-2 fractions. This fact prevents the mice bearing these types of alleles from being immunized against the cross-reacting tumours. If this result could be transposed to the human situation, it would explain the frequency of certain types of tumours in defined H-LA groups and could allow the prediction of high-risk groups.

Animals↗
PubMed2005

Suppression extends to major histocompatibility antigens linked to tolerizing minor histocompatibility antigens, but not the other way round.

'Active suppression', a mechanism of transplantation tolerance, can spread to newly introduced minor antigens once these antigens are linked to tolerizing antigens. We explored whether this suppression can extend to major histocompatibility (MHC) antigens and whether this phenomenon can be demonstrated once tolerance is induced to a MHC antigen. Mice were tolerized using donor bone marrow plus CD4 and CD8 monoclonal antibodies. The following strain combinations were used: AKR (H-2k) into CBA (H-2k), a multiple minor difference and B6 (H-2b) into B6(bm12) (H-2b), a MHC class II difference. Tolerance was tested by a donorskingraft. CBA mice tolerant to AKR received a second skin carrying either AKR antigens plus additional multiple minor antigens [F1(AKRxBalb.K)] or carrying additional minors and a MHC class I antigen (B10.AKM-H2M). B6(bm12) (H-2b) tolerant to B6 (H-2b) were grafted with skin from a Balb.B donor (Balb minors linked to the tolerizing class II antigen) or from a B10.A(3R) strain (a MHC class I antigen linked to the tolerizing class II antigen). CBA mice tolerant to AKR accepted F1(AKRxBalb.K) skin, whereas F1(CBAxBalb.K) were rejected. Rejection of B10.AKM/H2M skin by tolerant mice was delayed as compared with nontolerant mice. Tolerant and nontolerant B6(bm12) mice rejected Balb.B skin and B10.A(3R) skin within the same time. Thus, in this model, suppression was linked to minors. Alloreactivity against minors and majors could be suppressed. Suppression linked to a class II antigen could not be demonstrated.

Animals↗
PubMed2005

Immunotherapy of cancer through targeting of minor histocompatibility antigens.

Minor histocompatibility antigens are allogeneic targets of T-cell mediated graft-versus-tumour effects following allogeneic stem cell transplantation. Recent research has identified several minor histocompatibility antigens as tumour proteins and has also disclosed their unique properties in both the induction and the effector phase of graft-versus-tumour effects. Targeting tumour-specific minor histocompatibility antigens by adoptive immunotherapy will battle against tumour tolerance and evoke allo-immune responses, thereby enhancing graft-versus-tumour effects against leukaemia and solid tumours. Recently acquired knowledge of the role of donor immunisation status, new techniques in the generation of minor histocompatibility antigen-specific cytotoxic T lymphocytes in vitro, and innovative principles in vaccination will help to design clinical trials that exploit minor histocompatibility antigens in the immunotherapy of cancer.

Animals↗
PubMed1981

Of cows and men: a comparative study of histocompatibility antigens.

Bovine histocompatibility antigens cross-react highly with HLA antigens in comparison to their homologues in other nonprimate species. A panel of 34 anti-HLA monoclonal antibodies was tested for binding activity with lymphocytes from five breeds of cattle. Eleven antibodies demonstrated extensive cross-reactivity. Lymphocytes from several species of ungulate and subungulate were then tested with the same panel of antibodies. The buffalo and hyrax also displayed some cross-reactivity, though not as extensive as seen with the cattle lymphocytes. Other ungulates showed essentially no cross-reactivity. The significance of these results is discussed in terms of the structure and evolution of histocompatibility antigens.

Animals↗