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Gene Review

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

Homo sapiens

Synonyms: AS, HLAB, SPDA1
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Disease relevance of HLA-B


Psychiatry related information on HLA-B


High impact information on HLA-B


Chemical compound and disease context of HLA-B


Biological context of HLA-B


Anatomical context of HLA-B

  • 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 [24].
  • It is expressed on natural killer (NK) cells and T cells, and has been shown to inhibit cytolytic functions of these cells upon interacting with its ligand, HLA-B (Bw4) [25].
  • Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules [26].
  • Two cell lines showed a reduced level of one or both of the TAP messenger RNAs (mRNAs), and one of these showed a reduction of HLA-B and -C gene expression as well, but the others had detectable mRNA levels [27].
  • The healthy trophoblast does not express classical HLA-A and HLA-B products; therefore, an MHC-restricted recognition of trophoblast-presented Ags is unlikely [28].

Associations of HLA-B with chemical compounds

  • Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4(+) HLA-B [29].
  • The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families [30].
  • C4 is coded by duplicated genes between HLA-D and HLA-B loci in the major histocompatibility complex in man [31].
  • Eight combinations of HLA-B, DR, BF, C2, C4A, and C4B markers were found to occur in haplotypes at frequencies significantly higher than expected [32].
  • Signal peptides derived from certain HLA-B proteins with threonine in position 2 only marginally up-regulated HLA-E surface expression in .221 cells [33].

Physical interactions of HLA-B

  • None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4(+) HLA-B [29].
  • The TNF gene is encoded in the class III region of the HLA complex adjacent to HLA-B [34].
  • We used FastM to define a model for the experimentally verified NFkappaB/IRF1 regulatory module from the major histocompatibility complex (MHC) class I HLA-B gene promoter [35].
  • The HLA-B locus discloses a higher number of alleles and more complex serologic patterns than those observed for the HLA-A locus [36].
  • MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA-B gene [37].

Enzymatic interactions of HLA-B


Regulatory relationships of HLA-B


Other interactions of HLA-B

  • Assembly and maturation of HLA-A and HLA-B antigens in vivo [44].
  • We present evidence that HIV-1 selectively downregulates HLA-A and HLA-B but does not significantly affect HLA-C or HLA-E [45].
  • Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell-cell binding assay [29].
  • In humans, expression of the highly polymorphic classical HLA-A and HLA-B loci is suppressed, while expression of the nonclassical HLA-G locus is up-regulated at the maternal-fetal interface [46].
  • KIR3DL1 and KIR3DL2 are NK cell receptors for polymorphic HLA-B and -A determinants [47].

Analytical, diagnostic and therapeutic context of HLA-B


  1. DNA typing for HLA-A and HLA-B identifies disparities between patients and unrelated donors matched by HLA-A and HLA-B serology and HLA-DRB1. Prasad, V.K., Kernan, N.A., Heller, G., O'Reilly, R.J., Yang, S.Y. Blood (1999) [Pubmed]
  2. Genome sequencing analysis of the 1.8 Mb entire human MHC class I region. Shiina, T., Tamiya, G., Oka, A., Takishima, N., Inoko, H. Immunol. Rev. (1999) [Pubmed]
  3. Loss of HLA haplotype and B locus down-regulation in melanoma cell lines. Marincola, F.M., Shamamian, P., Alexander, R.B., Gnarra, J.R., Turetskaya, R.L., Nedospasov, S.A., Simonis, T.B., Taubenberger, J.K., Yannelli, J., Mixon, A. J. Immunol. (1994) [Pubmed]
  4. Locus-specific transcriptional control of HLA genes. Soong, T.W., Hui, K.M. J. Immunol. (1992) [Pubmed]
  5. Association of MHC Class I chain-related A (MIC-A) gene polymorphism with Type I diabetes. Gambelunghe, G., Ghaderi, M., Cosentino, A., Falorni, A., Brunetti, P., Falorni, A., Sanjeevi, C.B. Diabetologia (2000) [Pubmed]
  6. Identification of a telomeric boundary of the HLA region with potential for predisposition to human narcolepsy. Miyagawa, T., Hohjoh, H., Honda, Y., Juji, T., Tokunaga, K. Immunogenetics (2000) [Pubmed]
  7. Frequency of HLA-A and B alleles in early and late-onset Alzheimer's disease. Middleton, D., Mawhinney, H., Curran, M.D., Edwardson, J.A., Perry, R., McKeith, I., Morris, C., Ince, P.G., Neill, D. Neurosci. Lett. (1999) [Pubmed]
  8. Hepatitis B antigen and antibody in heroin users. Blanck, R.R., Ream, N., Conrad, M. Am. J. Gastroenterol. (1979) [Pubmed]
  9. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Martin, M.P., Gao, X., Lee, J.H., Nelson, G.W., Detels, R., Goedert, J.J., Buchbinder, S., Hoots, K., Vlahov, D., Trowsdale, J., Wilson, M., O'Brien, S.J., Carrington, M. Nat. Genet. (2002) [Pubmed]
  10. Pretransplantation blood transfusion revisited. van Twuyver, E., Mooijaart, R.J., ten Berge, I.J., van der Horst, A.R., Wilmink, J.M., Kast, W.M., Melief, C.J., de Waal, L.P. N. Engl. J. Med. (1991) [Pubmed]
  11. Relation between skin cancer and HLA antigens in renal-transplant recipients. Bouwes Bavinck, J.N., Vermeer, B.J., van der Woude, F.J., Vandenbroucke, J.P., Schreuder, G.M., Thorogood, J., Persijn, G.G., Claas, F.H. N. Engl. J. Med. (1991) [Pubmed]
  12. The benefit of exchanging donor kidneys among transplant centers. Opelz, G. N. Engl. J. Med. (1988) [Pubmed]
  13. Long-term follow-up in London Transplant Group recipients of cadaver renal allografts. The influence of HLA matching on transplant outcome. Festenstein, H., Doyle, P., Holmes, J. N. Engl. J. Med. (1986) [Pubmed]
  14. Bf and C4 phenotypes in patients with psoriasis. Wyatt, R.J., Wang, C., Hudson, E.C., Jones, R.M., Noah, P.W., Rosenberg, E.W. Acta dermato-venereologica. Supplementum. (1989) [Pubmed]
  15. Allogeneic bone-marrow transplantation in infantile malignant osteopetrosis. Sieff, C.A., Chessells, J.M., Levinsky, R.J., Pritchard, J., Rogers, D.W., Casey, A., Muller, K., Hall, C.M. Lancet (1983) [Pubmed]
  16. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Hetherington, S., Hughes, A.R., Mosteller, M., Shortino, D., Baker, K.L., Spreen, W., Lai, E., Davies, K., Handley, A., Dow, D.J., Fling, M.E., Stocum, M., Bowman, C., Thurmond, L.M., Roses, A.D. Lancet (2002) [Pubmed]
  17. Inverse correlation between expression of HLA-B and c-myc in uveal melanoma. Blom, D.J., Mooy, C.M., Luyten, G.P., Kerkvliet, S., Ouwerkerk, I., Zwinderman, A.H., Schrier, P.I., Jager, M.J. J. Pathol. (1997) [Pubmed]
  18. Genomic organization of a polymorphic duplicated region centromeric of HLA-B. Leelayuwat, C., Abraham, L.J., Tabarias, H., Christiansen, F.T., Dawkins, R.L. Immunogenetics (1992) [Pubmed]
  19. Genetic mapping of the 21-hydroxylase-deficiency gene within the HLA linkage group. Levine, L.S., Zachmann, M., New, M.I., Prader, A., Pollack, M.S., O'Neill, G.J., Yang, S.Y., Oberfield, S.E., Dupont, B. N. Engl. J. Med. (1978) [Pubmed]
  20. Class I-like HLA genes map telomeric to the HLA-A2 locus in human cells. Orr, H.T., DeMars, R. Nature (1983) [Pubmed]
  21. Unusual HLA-B alleles in two tribes of Brazilian Indians. Belich, M.P., Madrigal, J.A., Hildebrand, W.H., Zemmour, J., Williams, R.C., Luz, R., Petzl-Erler, M.L., Parham, P. Nature (1992) [Pubmed]
  22. Isolation and N-terminal amino acid sequence of membrane-bound human HLA-A and HLA-B antigens. Bridgen, J., Snary, D., Crumpton, M.J. Nature (1976) [Pubmed]
  23. A new cluster of genes within the human major histocompatibility complex. Spies, T., Blanck, G., Bresnahan, M., Sands, J., Strominger, J.L. Science (1989) [Pubmed]
  24. 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]
  25. Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C. Fry, A.M., Lanier, L.L., Weiss, A. J. Exp. Med. (1996) [Pubmed]
  26. Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule. Chen, B.P., Madrigal, A., Parham, P. J. Exp. Med. (1990) [Pubmed]
  27. Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma. Kurokohchi, K., Carrington, M., Mann, D.L., Simonis, T.B., Alexander-Miller, M.A., Feinstone, S.M., Akatsuka, T., Berzofsky, J.A. Hepatology (1996) [Pubmed]
  28. Recognition of nonclassical HLA class I antigens by gamma delta T cells during pregnancy. Barakonyi, A., Kovacs, K.T., Miko, E., Szereday, L., Varga, P., Szekeres-Bartho, J. J. Immunol. (2002) [Pubmed]
  29. The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer. Khakoo, S.I., Geller, R., Shin, S., Jenkins, J.A., Parham, P. J. Exp. Med. (2002) [Pubmed]
  30. Extended major histocompatibility complex haplotypes in type I diabetes mellitus. Raum, D., Awdeh, Z., Yunis, E.J., Alper, C.A., Gabbay, K.H. J. Clin. Invest. (1984) [Pubmed]
  31. The origin of the very variable haemolytic activities of the common human complement component C4 allotypes including C4-A6. Dodds, A.W., Law, S.K., Porter, R.R. EMBO J. (1985) [Pubmed]
  32. Extended HLA/complement allele haplotypes: evidence for T/t-like complex in man. Awdeh, Z.L., Raum, D., Yunis, E.J., Alper, C.A. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  33. HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. Lee, N., Goodlett, D.R., Ishitani, A., Marquardt, H., Geraghty, D.E. J. Immunol. (1998) [Pubmed]
  34. Mapping the HLA association in Behçet's disease: a role for tumor necrosis factor polymorphisms? Ahmad, T., Wallace, G.R., James, T., Neville, M., Bunce, M., Mulcahy-Hawes, K., Armuzzi, A., Crawshaw, J., Fortune, F., Walton, R., Stanford, M.R., Welsh, K.I., Marshall, S.E., Jewell, D.P. Arthritis Rheum. (2003) [Pubmed]
  35. Functional promoter modules can be detected by formal models independent of overall nucleotide sequence similarity. Klingenhoff, A., Frech, K., Quandt, K., Werner, T. Bioinformatics (1999) [Pubmed]
  36. HLA-B*1303: a new example of poor correlation between serology and structure. Balas, A., García-Sánchez, F., Vicario, J.L. Hum. Immunol. (1996) [Pubmed]
  37. MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis. Glas, J., Martin, K., Brünnler, G., Kopp, R., Folwaczny, C., Weiss, E.H., Albert, E.D. Tissue Antigens (2001) [Pubmed]
  38. Identification of CCAAT displacement protein (CDP/cut) as a locus-specific repressor of major histocompatibility complex gene expression in human tumor cells. Snyder, S.R., Wang, J., Waring, J.F., Ginder, G.D. J. Biol. Chem. (2001) [Pubmed]
  39. 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]
  40. The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors. Della Chiesa, M., Vitale, M., Carlomagno, S., Ferlazzo, G., Moretta, L., Moretta, A. Eur. J. Immunol. (2003) [Pubmed]
  41. Lack of CIITA expression is central to the absence of antigen presentation functions of trophoblast cells and is caused by methylation of the IFN-gamma inducible promoter (PIV) of CIITA. van den Elsen, P.J., van der Stoep, N., Viëtor, H.E., Wilson, L., van Zutphen, M., Gobin, S.J. Hum. Immunol. (2000) [Pubmed]
  42. High frequency of allele-specific down-regulation of HLA class I expression in uveal melanoma cell lines. Hurks, H.M., Metzelaar-Blok, J.A., Mulder, A., Claas, F.H., Jager, M.J. Int. J. Cancer (2000) [Pubmed]
  43. High expression of HLA-A2 on an oral squamous cell carcinoma with down-regulated transporter for antigen presentation. Matsui, M., Ikeda , M., Akatsuka, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  44. Assembly and maturation of HLA-A and HLA-B antigens in vivo. Krangel, M.S., Orr, H.T., Strominger, J.L. Cell (1979) [Pubmed]
  45. The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Cohen, G.B., Gandhi, R.T., Davis, D.M., Mandelboim, O., Chen, B.K., Strominger, J.L., Baltimore, D. Immunity (1999) [Pubmed]
  46. Identification of a novel MHC class I gene, Mamu-AG, expressed in the placenta of a primate with an inactivated G locus. Boyson, J.E., Iwanaga, K.K., Golos, T.G., Watkins, D.I. J. Immunol. (1997) [Pubmed]
  47. Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. Gardiner, C.M., Guethlein, L.A., Shilling, H.G., Pando, M., Carr, W.H., Rajalingam, R., Vilches, C., Parham, P. J. Immunol. (2001) [Pubmed]
  48. 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]
  49. Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes. D'Andrea, A., Chang, C., Franz-Bacon, K., McClanahan, T., Phillips, J.H., Lanier, L.L. J. Immunol. (1995) [Pubmed]
  50. Alloantibody-mediated class I signal transduction in endothelial cells and smooth muscle cells: enhancement by IFN-gamma and TNF-alpha. Bian, H., Reed, E.F. J. Immunol. (1999) [Pubmed]
  51. Fractionation of membrane proteins on phenylboronic acid-agarose. Williams, G.T., Johnstone, A.P., Dean, P.D. Biochem. J. (1982) [Pubmed]
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