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Gene Review

HLA-A  -  major histocompatibility complex, class I, A

Homo sapiens

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Disease relevance of HLA-A


Psychiatry related information on HLA-A


High impact information on HLA-A

  • Solution of the crystal structures of the MHC class-I alleles A2 and Aw68 has identified a putative antigen-combining site whose overall dimensions were quite similar between the two structures [11].
  • BACKGROUND: Successful engraftment of hematopoietic stem cells from unrelated donors is influenced by disparities between the donor and recipient for HLA-A, B, and C alleles [12].
  • Three separate validations-comparison with 54 genes screened for SNPs independently, verification of HLA-A polymorphisms and restriction fragment length polymorphism (RFLP) testing-verified 70%, 89% and 71% of our predicted SNPs, respectively [13].
  • METHODS: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation [14].
  • METHODS: We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens [15].

Chemical compound and disease context of HLA-A


Biological context of HLA-A


Anatomical context of HLA-A

  • Such class I molecules have also been found on the surface of human T lymphocytes and, in one case, shown to be linked to HLA-A [25].
  • The outermost layer of the human placenta is devoid of classical class I human leukocyte antigens (HLA-A, HLA-B, and HLA-C) and class II proteins (HLA-DR, HLA-DQ, and HLA-DP) [26].
  • Here, we demonstrate that human NK cells also express C-type lectin receptors that influence recognition of polymorphic HLA-A, HLA-B, and HLA-C molecules [27].
  • It is also clear that complex maternal immunologic responses, including antibodies to red blood cell antigens, HLA-A, HLA-B, HLA-C, and HLA-D antigens, and cell-mediated responses such as proliferation, lymphokines, cytotoxicity, and suppressor cells, are generated to a variety of paternal antigenic determinants [28].
  • Therefore, our results suggest that the selective down-regulation of HLA-A and HLA-Bw6 allospecificities associated with HLA-Bw4 preservation provides leukemic cells with an escape mechanism not only from cytotoxic T lymphocytes (CTLs), but also from NK cells [29].

Associations of HLA-A with chemical compounds

  • The uniformity of oligosaccharide structure associated with different HLA-A, -B, and -C products and the relative lack of heterogeneity for any given allotype are unusual features for a mammalian glycoprotein [30].
  • In this report we show that ligation of class I molecules with Abs to distinct HLA-A locus and HLA-B locus molecules results in increased tyrosine phosphorylation of intracellular proteins and induction of fibroblast growth factor receptor expression on endothelial and smooth muscle cells [31].
  • Allotypes encoded by the HLA-A and -B loci have two predominant glycan structures that were almost exclusively di-sialylated [30].
  • In addition Rg, Ch, BF, C2, HLA-A, B, C, DR, and GLO were determined [32].
  • The following markers were studied: HLA-A, B, C,DR, DQ(MB), DP(SB), complement allotypes C4 and Bf and glyoxalase I polymorphism [33].

Physical interactions of HLA-A

  • S100A8/A9 complexes, as well as S100A9 homodimers, stimulated the production of proinflammatory cytokines, such as tumor necrosis factor alpha, by purified monocytes and in vitro-differentiated macrophages [34].
  • Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8 [35].
  • RNase T1 protection and immunoprecipitation experiments demonstrate that recombinant protein A1 specifically binds the 3'-end regions of both beta-globin and Ad-2 introns [36].
  • Retroviral introduction of a Fab-based chimeric receptor specific for MAGE-A1/HLA-A1 into primary human T lymphocytes resulted in binding of relevant peptide/MHC complexes [37].
  • Therefore, it seems reasonable to conclude that beta2-microglobulin is of importance for intracellular transport of newly synthesized HLA-A, -B, and -C antigens [38].

Enzymatic interactions of HLA-A

  • Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/split antigen level for HLA-A and -B [39].

Regulatory relationships of HLA-A

  • An inverse relationship was established between JAR and JEG-3: HLA-A, -B, and -G are methylated and repressed in JAR, whereas in JEG-3, HLA-A is methylated and repressed but HLA-B and -G are partially methylated and transcribed [40].
  • Accordingly, the aim of this study was to define the behavior of HLA-G once it is co-expressed into an HLA-A, -B, -C and -E+ cell line [41].
  • The aberrant HLA-E expression might be of particular biological relevance in those HLA tumor phenotypes that express a single HLA-A allele when NK inhibition is markedly reduced due to the downregulation of HLA-B and -C alleles [42].
  • We show that the HLA-A promoter activity cannot be induced by interferon-gamma (IFN-gamma) and that exogenous MHC class II transactivator CIITA is able to induce HLA class I promoter activity in these cells [43].
  • METHODS: 65 rheumatoid arthritis patients and 255 controls were typed for C4 allotypes and HLA-A, B, C, DR, and DQ antigens [44].

Other interactions of HLA-A

  • Assembly and maturation of HLA-A and HLA-B antigens in vivo [45].
  • The third expressed non-A, -B, and -C class I gene, HLA-E, is located between HLA-A and HLA-C (4) [46].
  • In comparison with HLA-A and -B, HLA-C alleles are more closely related to each other, there being less variation in residues of the antigen recognition site and more variation at other positions [47].
  • The haplotypes examined comprise the following highly polymorphic markers: the serological marker HLA-A and the microsatellites D6S248, D6S265, HLA-F, and D6S105 [48].
  • To elucidate the biological importance of HLA-DQB1, we conducted a retrospective analysis of 449 HLA-A, -B, and -DR serologically matched unrelated donor transplants [49].

Analytical, diagnostic and therapeutic context of HLA-A

  • CONCLUSIONS: Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens [15].
  • Sequence analysis and transfection studies indicate that three genes, in addition to those encoding the HLA-A, -B, and -C antigens can direct the synthesis of a class I alpha protein (4, 5, 21) [46].
  • Fifty-three patients with SCA underwent complete HLA typing at both HLA class I (HLA-A, B) and HLA class II (HLA-DR, DQ, DP) loci [50].
  • We designed a matched case-control study and employed DNA sequencing methods to evaluate the role of HLA-C disparity in 21 patients who experienced graft failure (cases) following transplantation with unmanipulated marrow from either HLA-A, B serologically matched, DRB1 matched (n = 14) or single locus mismatched (n = 7) unrelated donors [51].
  • PATIENTS AND METHODS: We performed class I (HLA-A, HLA-B, and HLA-C) serotyping on patients enrolled onto Southwest Oncology Group Trial 9035, a randomized, observation-controlled, phase III trial of adjuvant Melacine [52].


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  14. The economic implications of HLA matching in cadaveric renal transplantation. Schnitzler, M.A., Hollenbeak, C.S., Cohen, D.S., Woodward, R.S., Lowell, J.A., Singer, G.G., Tesi, R.J., Howard, T.K., Mohanakumar, T., Brennan, D.C. N. Engl. J. Med. (1999) [Pubmed]
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  17. The effect of ethnicity on major histocompatibility complex complement allotypes and extended haplotypes in patients with systemic lupus erythematosus. Schur, P.H., Marcus-Bagley, D., Awdeh, Z., Yunis, E.J., Alper, C.A. Arthritis Rheum. (1990) [Pubmed]
  18. HLA and complement allotypes in Type 1 (insulin-dependent) diabetes. McCluskey, J., McCann, V.J., Kay, P.H., Zilko, P.J., Christiansen, F.T., O'Neill, G.J., Dawkins, R.L. Diabetologia (1983) [Pubmed]
  19. Lithocholic acid inhibits the expression of HLA class I genes in colon adenocarcinoma cells. Differential effect on HLA-A, -B and -C loci. Arvind, P., Papavassiliou, E.D., Tsioulias, G.J., Duceman, B.W., Lovelace, C.I., Geng, W., Staiano-Coico, L., Rigas, B. Mol. Immunol. (1994) [Pubmed]
  20. Association of herpes simplex virus-induced erythema multiforme with the human leukocyte antigen DQw3. Kämpgen, E., Burg, G., Wank, R. Archives of dermatology. (1988) [Pubmed]
  21. HLA-DR specificities among black Americans with juvenile-onset diabetes. Rodey, G.E., White, N., Frazer, T.E., Duquesnoy, R.J., Santiago, J.V. N. Engl. J. Med. (1979) [Pubmed]
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  27. CD94 and a novel associated protein (94AP) form a NK cell receptor involved in the recognition of HLA-A, HLA-B, and HLA-C allotypes. Phillips, J.H., Chang, C., Mattson, J., Gumperz, J.E., Parham, P., Lanier, L.L. Immunity (1996) [Pubmed]
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  30. Unusual uniformity of the N-linked oligosaccharides of HLA-A, -B, and -C glycoproteins. Barber, L.D., Patel, T.P., Percival, L., Gumperz, J.E., Lanier, L.L., Phillips, J.H., Bigge, J.C., Wormwald, M.R., Parekh, R.B., Parham, P. J. Immunol. (1996) [Pubmed]
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  33. Recombination between HLA-A and C and between HLA-B and complement locus C4 in the same individual. Thomsen, M., Cambon-Thomsen, A., Abbal, M., Calot, M., Arnaud, J., Ohayon, E. Tissue Antigens (1985) [Pubmed]
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  37. A phage display selected fab fragment with MHC class I-restricted specificity for MAGE-A1 allows for retargeting of primary human T lymphocytes. Willemsen, R.A., Debets, R., Hart, E., Hoogenboom, H.R., Bolhuis, R.L., Chames, P. Gene Ther. (2001) [Pubmed]
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  40. Methylation status and transcriptional expression of the MHC class I loci in human trophoblast cells from term placenta. Guillaudeux, T., Rodriguez, A.M., Girr, M., Mallet, V., Ellis, S.A., Sargent, I.L., Fauchet, R., Alsat, E., Le Bouteiller, P. J. Immunol. (1995) [Pubmed]
  41. HLA-G1 co-expression boosts the HLA class I-mediated NK lysis inhibition. Riteau, B., Menier, C., Khalil-Daher, I., Martinozzi, S., Pla, M., Dausset, J., Carosella, E.D., Rouas-Freiss, N. Int. Immunol. (2001) [Pubmed]
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  46. Chromosomal organization of the human major histocompatibility complex class I gene family. Koller, B.H., Geraghty, D.E., DeMars, R., Duvick, L., Rich, S.S., Orr, H.T. J. Exp. Med. (1989) [Pubmed]
  47. Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C. Zemmour, J., Parham, P. J. Exp. Med. (1992) [Pubmed]
  48. Haplotype analysis in Australian hemochromatosis patients: evidence for a predominant ancestral haplotype exclusively associated with hemochromatosis. Jazwinska, E.C., Pyper, W.R., Burt, M.J., Francis, J.L., Goldwurm, S., Webb, S.I., Lee, S.C., Halliday, J.W., Powell, L.W. Am. J. Hum. Genet. (1995) [Pubmed]
  49. Definition of HLA-DQ as a transplantation antigen. Petersdorf, E.W., Longton, G.M., Anasetti, C., Mickelson, E.M., Smith, A.G., Martin, P.J., Hansen, J.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  50. Evidence for HLA-related susceptibility for stroke in children with sickle cell disease. Styles, L.A., Hoppe, C., Klitz, W., Vichinsky, E., Lubin, B., Trachtenberg, E. Blood (2000) [Pubmed]
  51. Association of HLA-C disparity with graft failure after marrow transplantation from unrelated donors. Petersdorf, E.W., Longton, G.M., Anasetti, C., Mickelson, E.M., McKinney, S.K., Smith, A.G., Martin, P.J., Hansen, J.A. Blood (1997) [Pubmed]
  52. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen expression on outcome. Sosman, J.A., Unger, J.M., Liu, P.Y., Flaherty, L.E., Park, M.S., Kempf, R.A., Thompson, J.A., Terasaki, P.I., Sondak, V.K. J. Clin. Oncol. (2002) [Pubmed]
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