Role of MICA in the immune response to transplants

Department of Internal Medicine, Transplantation Immunology Division, University of Texas Southwestern Medical Center, Dallas, TX 75390-8886, USA.
Tissue Antigens (Impact Factor: 2.14). 09/2010; 76(3):171-6. DOI: 10.1111/j.1399-0039.2010.01527.x
Source: PubMed


Among the cell surface antigens that can elicit an immune response in transplant recipients MICA antigens occupy a special place. They are similar to human leukocyte antigens (HLAs) while being very different from them. They are not as polymorphic and their quantity is smaller. In consequence, the impact of MICA antigens in transplantation is not as dramatic. However, our early guess that these ligands of NKG2D could elicit antibodies and cell-mediated immunity has been definitely confirmed. Careful analysis with MICA transfectant cells, for absorption and elution, established the specificity of the epitopes involved. Typing of recipients and donors by sequencing the MICA alleles has established that de novo antibodies produced in kidney transplant recipients are directed at mismatched MICA epitopes and are associated with acute rejection and chronic transplant failure. Acute graft-versus-host disease was observed in stem cell recipients who were mismatched for MICA.

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    • "In our combined opinion, future studies should focus on association of HLA and MICA polymorphism with diseases, e.g. by looking at HLA and MICA alleles which are closely linked and crucial in immune responses see [1] [2] [70]. In addition, HLA and MICA polymorphisms are also important in transplantation as the success rate of transplantation is dependent on the degree of HLA and MICA matching between donor and recipient [4] [76] [77]. The HLA and MICA data presented here suggest that the feasibility of finding suitable donors for Maori and Polynesian patients is within their own ethnic group(s), as they share a number of common and unique HLA and MICA alleles. "
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    ABSTRACT: Data from HLA typing studies have made significant contributions to genetic theories about the Austronesian diaspora and the health of descendant populations. To help further unravel pattern and process elements, we have typed HLA and MICA loci at high resolution in DNA samples from well defined groups of Maori and Polynesian individuals. Our results show a restricted set of HLA class I alleles compared with other well characterised populations. In contrast, the class II HLA-DRB1 locus seems to be diverse in Maori and Polynesians and both groups show high frequencies of HLA-DRB1∗04:03, -DRB1∗08:03, -DRB1∗09:01 and -DRB1∗12:01. Our survey also provides the first ever MICA datasets for Polynesians and reveal unusual distributions and associations with the HLA-B locus. Overall, our data provide further support for a hybrid origin for Maori and Polynesians. One novel feature of our study is the finding that the gene sequence of the HLA-B∗40:10 allele in Polynesians is a recombinant of HLA-B∗55:02 and -B∗40:01. HLA-B∗40:10 is in close association with HLA-C∗04:03, an allele identified as a hybrid of HLA-C∗04 and -C∗02. In this respect, our data resemble those reports on Amerindian tribes where inter-allele recombination has been a common means of generating diversity. However, we emphasize that Amerindian gene content per se is only a very minor element of the overall Polynesian genepool. The wider significance of HLA and MICA allele frequencies across the Pacific for modern day health is also discussed in terms of the frequency relative to reference populations of disease known to be associated with specific HLA and MICA markers. Thus, Polynesians and Maori are largely unaffected by "European autoimmune diseases" such as ankylosing spondylitis, uveitis and coeliacs disease, yet there are several Maori- and Polynesian-specific autoimmune diseases where the HLA and MICA associations are still to be determined.
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    ABSTRACT: H60a is a minor histocompatibility antigen expressed in BALB and 129/Sv but not C57BL/6 mouse strains. The majority of CD8+ T cells in C57BL/6 mice responding to BALB.B splenocytes are specific for H60a. Interestingly, H60a is expressed constitutively on tumour cells, but its nature as a tumour rejection antigen, as a parallel to its function as a transplant rejection antigen, has not been studied. In this report, we show that tumour cells that constitutively express H60a at the cell surface can be recognized by H60a-specific T cells. Furthermore, when H60a-expressing sarcoma cell lines are transplanted into C57BL/6 mice, H60a-specific T cells can be found at high percentages among the tumour-infiltrating CD8+ T cells. These findings were seen in C57BL/6 but not F1 (C57BL/6×129) mice (which express H60a), suggesting that endogenous tolerance mechanisms suppress the antigenic properties of H60a. Our findings have implications for the generation of tumour vaccines against human natural killer group 2D ligands, such as MHC class I chain-like gene A, that are also transplantation antigens.
    Preview · Article · Mar 2011 · Immunology
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    ABSTRACT: Even when kidney allografts are well matched for human leukocyte antigen (HLA) and anti-HLA antibodies are not detected, graft rejection can still occur. There is evidence that some patients who lose their graft have antibodies specific for major histocompatibility complex (MHC) class I-related chain A (MICA) antigens. We investigated whether mismatching MICA alleles associates with MICA antibody production and graft rejection or dysfunction. MICA and HLA antibody screening in 442 recipients was performed, and specificities were confirmed in a subgroup of 227 recipients using single-antigen multiplex technology. For assignment of MICA antibody specificity, we used three independent assays. In addition, MICA alleles of 227 recipients and donors were determined by DNA sequencing. In all, 17 patients (7.5%) had MICA antibodies, and 13 patients (6%) developed MICA donor-specific antibodies (DSA). Multivariate analysis revealed MICA mismatching, as an independent significant factor associated with the presence of MICA antibodies (p = 0.009), and 14 mismatched MICA residues significantly correlated with MICA antibody production. MICA and HLA antibodies significantly associated with acute rejection (AR) and MICA DSA and HLA DSA correlated with decreased graft function by univariate and multivariate analysis. We conclude that mismatching for MICA epitopes in renal transplantation is a mechanism leading to production of MICA antibodies that associate with AR and graft dysfunction.
    Full-text · Article · May 2011 · Human immunology
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