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Gene Review

H2-Aa  -  histocompatibility 2, class II antigen A,...

Mus musculus

Synonyms: A alpha, Aalpha, H-2 class II histocompatibility antigen, A-B alpha chain, H-2 class II histocompatibility antigen, A-D alpha chain, H-2 class II histocompatibility antigen, A-F alpha chain, ...
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Disease relevance of H2-Aa


Psychiatry related information on H2-Aa

  • The role of A alpha chain is also implied by the permissiveness of E kappa alpha Aq beta but not Aq alpha Aq beta molecules in the deletion of V beta 6+ T cells [6].
  • Hyperphosphorylated tau, the major component of the paired helical filaments of Alzheimer's disease, was found to accumulate in the brains of mice in which the calcineurin A alpha gene was disrupted [calcineurin A alpha knockout (CNA alpha -/-)] [7].

High impact information on H2-Aa


Chemical compound and disease context of H2-Aa


Biological context of H2-Aa

  • Indeed, the A alpha and A beta chains of the I-A antigens appear to exhibit normal behavior by the criteria of serology and two dimensional gel analysis [13].
  • The dimorphic allelic lineages are in marginally detectable linkage disequilibrium with the exon 2 sequences, particularly in H2Aa, thus lending further support to the coevolution hypothesis [14].
  • We report nucleotide sequences for the A alpha chain cDNAs of the k, r, and s haplotypes, which, when compared to previously published A alpha sequences, demonstrate the existence of one k-specific amino acid residue and of another present only in the k and r haplotypes [15].
  • The murine Ia alpha chains, E alpha and A alpha, show a surprising degree of sequence homology [16].
  • To account for these observations, it is proposed that during evolution of the mouse H-2 complex, in addition to gene duplication of ancestral gene(s) to yield the genes encoding E alpha A alpha, A beta, and E beta polypeptide chains, further gene duplication occurred, forming multiple copies of genes encoding each Ia polypeptide chain [17].

Anatomical context of H2-Aa

  • Significant proliferative responses of F-MuLV envelope-specific, H-2a/b T cells were observed when the T cells were stimulated with antigen-pulsed peritoneal exudate cells (PEC) having the b allele at the K, A beta, A alpha, and E beta loci of the H-2 [18].
  • These mice feature immune system perturbations like those of Aalpha and Abeta knockout animals, notably a dearth of CD4(+) lymphocytes in the thymus and spleen [19].
  • Analysis of the mutant cell lines has allowed us to assign the reactivity of each mAb to either the A alpha- or the A beta-polypeptide [20].
  • We have compared the presentation of five different epitopes derived from hen egg white lysozyme (HEL) to Ak-restricted T hybridomas by rat-2 fibroblasts transfected with A alpha k and A beta k (RKK) and RKK cells supertransfected with the mouse invariant chain (RKKI) [21].
  • By contrast, although C57BL/6 gave a good response, the mutant strain was unable to generate cytotoxic T lymphocytes to the male-specific H-Y antigen--a response under I-A subregion Ir gene control, which now must be considered to be the Ia-1 gene [22].

Associations of H2-Aa with chemical compounds

  • Here we report that the expression of I-Ak (A alpha kA beta k) in transgenic NOD mice can also prevent insulitis, and that this protection is seen not only when the I-A beta-chain has aspartic acid as residue 57, but also when this residue is serine [23].
  • Constructs containing 5' deletion mutations of the A alpha promoter attached to the bacterial chloramphenicol acetyl transferase gene were used to delineate the minimum 5' flanking sequences required for promoter activity, and for inducibility by IFN-gamma and TNF-alpha [24].
  • Class II antigens display extensive genetic polymorphism, the main part of which resides in the NH2-terminal domains of the A alpha, A beta and E beta chains [25].
  • Induction of A alpha-specific mRNA was sensitive to the protein synthesis inhibitor cycloheximide [26].
  • To test whether this residue actually was important physiologically, a lysine codon was created in a recombinant A beta gene possessing the amino-terminal sequence of the kappa haplotype, and the ability of this mutant chain to be expressed with various mouse A alpha-chains was examined [27].

Physical interactions of H2-Aa


Regulatory relationships of H2-Aa


Other interactions of H2-Aa

  • Incubation of T cells with the A alpha (g7)63-82YC peptide resulted in up-regulation of IL-2R alpha chain expression and induction of IFN-gamma secretion [32].
  • C3H.Q lacks functional H2-E molecules and share H2-Aalpha with C3H.NB [33].
  • The results obtained demonstrate that the regions between residues 69 to 76 of the A alpha k chain and the regions between residues 63 to 67 and 75 to 78 of the A beta k-chain exert a dominant effect on the presentation of lysozyme peptides by I-Ak to the T cell hybridomas in our panel [34].
  • We show that embryonic day (E)9.5 A alpha/A gamma embryos display severe malformations, similar to those already described in retinaldehyde dehydrogenase 2 null mutants [35].
  • The hindbrain of E8.5 A alpha/A gamma embryos shows a posterior expansion of rhombomere 3 and 4 (R3 and R4) markers, but fails to express kreisler, a normal marker of R5 and R6 [35].

Analytical, diagnostic and therapeutic context of H2-Aa

  • Northern blot analyses indicated that one I-A-, I-E+ tumor strongly expressed A alpha, E alpha, and E beta mRNAs but possessed only a weak expression of A beta mRNA [3].
  • By immunoprecipitation and two-dimensional analysis of Ia molecules from F1 spleen cells, we could independently map the reactivities of the mAb as being determined by the A alpha or A beta chain [36].
  • Further, we have used our high-pressure liquid chromatography tryptic peptide map technique to formally map the genes encoding Aalpha, Abeta, and Ebeta to the I-A subregion using recombinant and F1 hybrid mice [37].
  • HPLC peptide map comparisons of A alpha d, A beta d and the 22Kd polypeptides demonstrated that the 22Kd polypeptide has extensive homology with A alpha d [38].
  • We have compared the tryptic peptide fingerprints of the A alpha, A beta, E alpha, and E beta subunits encoded by four wild-derived H-2 complexes expressing A molecules closely related to Ak [39].


  1. MHC-II-independent CD4+ T cells induce colitis in immunodeficient RAG-/- hosts. Trobonjaca, Z., Leithäuser, F., Möller, P., Bluethmann, H., Koezuka, Y., MacDonald, H.R., Reimann, J. J. Immunol. (2001) [Pubmed]
  2. MHC class II-independent CD25+ CD4+ CD8alpha beta+ alpha beta T cells attenuate CD4+ T cell-induced transfer colitis. Krajina, T., Leithäuser, F., Reimann, J. Eur. J. Immunol. (2004) [Pubmed]
  3. Imbalanced MHC class II molecule expression at surface of murine B cell lymphomas. Zijlstra, M., Vasmel, W.L., Voormanns, M., de Goede, R.E., Schoenmakers, H.J., Nieland, J., Slater, R.M., Melief, C.J. J. Exp. Med. (1986) [Pubmed]
  4. Single amino acid mutations in the murine MHC class II A beta cytoplasmic domain abrogate antigen presentation. Laufer, T.M., Smiley, S.T., Ranger, A., Clements, V.K., Ostrand-Rosenberg, S., Glimcher, L.H. J. Immunol. (1997) [Pubmed]
  5. Molecular cloning, expression, and function of osteoclastic calcineurin Aalpha. Sun, L., Moonga, B.S., Lu, M., Zaidi, N., Iqbal, J., Blair, H.C., Epstein, S., Abe, E., Troen, B.R., Huang, C.L., Zaidi, M. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  6. MHC class II A alpha and E alpha molecules determine the clonal deletion of V beta 6+ T cells. Studies with recombinant and transgenic mice. Anderson, G.D., Banerjee, S., David, C.S. J. Immunol. (1989) [Pubmed]
  7. Cytoskeletal changes in the brains of mice lacking calcineurin A alpha. Kayyali, U.S., Zhang, W., Yee, A.G., Seidman, J.G., Potter, H. J. Neurochem. (1997) [Pubmed]
  8. Intracellular competition for component chains determines class II MHC cell surface phenotype. Sant, A.J., Germain, R.N. Cell (1989) [Pubmed]
  9. Functional sites on Ia molecules: a molecular dissection of A alpha immunogenicity. Landais, D., Waltzinger, C., Beck, B.N., Staub, A., McKean, D.J., Benoist, C., Mathis, D. Cell (1986) [Pubmed]
  10. Regions of allelic hypervariability in the murine A alpha immune response gene. Benoist, C.O., Mathis, D.J., Kanter, M.R., Williams, V.E., McDevitt, H.O. Cell (1983) [Pubmed]
  11. A DNA binding protein regulated by IL-4 and by differentiation in B cells. Boothby, M., Gravallese, E., Liou, H.C., Glimcher, L.H. Science (1988) [Pubmed]
  12. Bleomycin-induced pulmonary fibrosis in fibrinogen-null mice. Hattori, N., Degen, J.L., Sisson, T.H., Liu, H., Moore, B.B., Pandrangi, R.G., Simon, R.H., Drew, A.F. J. Clin. Invest. (2000) [Pubmed]
  13. Intragenic recombination in an E beta gene for a murine Ia antigen. Plunkett, M.L., Coligan, J.E., David, C.S., Freed, J.H. J. Exp. Med. (1982) [Pubmed]
  14. Patterned variation in murine MHC promoters. Mitchison, N.A., Roes, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  15. A molecular basis for the Ia.2 and Ia.19 antigenic determinants. Landais, D., Matthes, H., Benoist, C., Mathis, D. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  16. The murine Ia alpha chains, E alpha and A alpha, show a surprising degree of sequence homology. Benoist, C.O., Mathis, D.J., Kanter, M.R., Williams, V.E., McDevitt, H.O. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  17. Cross-reactions of anti-I-Ek monoclonal antibodies with subsets of I-Ab molecules. Lafuse, W.P., Pierres, M., David, C.S. Transplantation (1983) [Pubmed]
  18. Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes. Miyazawa, M., Nishio, J., Chesebro, B. J. Exp. Med. (1988) [Pubmed]
  19. Mice lacking all conventional MHC class II genes. Madsen, L., Labrecque, N., Engberg, J., Dierich, A., Svejgaard, A., Benoist, C., Mathis, D., Fugger, L. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  20. Characterization of cell lines expressing mutant I-Ab and I-Ak molecules allows the definition of distinct serologic epitopes on A alpha and A beta polypeptides. Beck, B.N., Buerstedde, J.M., Krco, C.J., Nilson, A.E., Chase, C.G., McKean, D.J. J. Immunol. (1986) [Pubmed]
  21. Epitope-specific enhancement of antigen presentation by invariant chain. Momburg, F., Fuchs, S., Drexler, J., Busch, R., Post, M., Hämmerling, G.J., Adorini, L. J. Exp. Med. (1993) [Pubmed]
  22. Ir gene function in an I-A subregion mutant B6.C-H-2bm12. Michaelides, M., Sandrin, M., Morgan, G., McKenzie, I.F., Ashman, R., Melvold, R.W. J. Exp. Med. (1981) [Pubmed]
  23. Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice. Miyazaki, T., Uno, M., Uehira, M., Kikutani, H., Kishimoto, T., Kimoto, M., Nishimoto, H., Miyazaki, J., Yamamura, K. Nature (1990) [Pubmed]
  24. cis-acting sequences required for class II gene regulation by interferon gamma and tumor necrosis factor alpha in a murine macrophage cell line. Freund, Y.R., Dedrick, R.L., Jones, P.P. J. Exp. Med. (1990) [Pubmed]
  25. The Eb beta gene may have acted as the donor gene in a gene conversion-like event generating the Abm 12 beta mutant. Denaro, M., Hammerling, U., Rask, L., Peterson, P.A. EMBO J. (1984) [Pubmed]
  26. Induction of macrophage Ia antigen expression by rIFN-gamma and down-regulation by IFN-alpha/beta and dexamethasone are mediated by changes in steady-state levels of Ia mRNA. Fertsch, D., Schoenberg, D.R., Germain, R.N., Tou, J.Y., Vogel, S.N. J. Immunol. (1987) [Pubmed]
  27. Cell surface expression of hybrid murine/human MHC class II beta alpha dimers. Key influence of residues in the amino-terminal portion of the beta 1 domain. Lechler, R.I., Sant, A.J., Braunstein, N.S., Sekaly, R., Long, E., Germain, R.N. J. Immunol. (1990) [Pubmed]
  28. Expression of MHC class II A alpha k transgene. Pairing with endogenous beta-chain is dependent upon affinity and competition. Martin, J., Wei, B.Y., David, C.S. Transplantation (1993) [Pubmed]
  29. Distinct IL-4 response mechanisms of the MHC gene A alpha in different mouse B cell lines. Whitley, M.Z., Cheng, H.L., Tomasi, T.B., Boothby, M. Mol. Immunol. (1993) [Pubmed]
  30. Identification of a conserved lipopolysaccharide-plus-interleukin-4-responsive element located at the promoter of germ line epsilon transcripts. Rothman, P., Li, S.C., Gorham, B., Glimcher, L., Alt, F., Boothby, M. Mol. Cell. Biol. (1991) [Pubmed]
  31. Decorin reverses the repressive effect of autocrine-produced TGF-beta on mouse macrophage activation. Comalada, M., Cardó, M., Xaus, J., Valledor, A.F., Lloberas, J., Ventura, F., Celada, A. J. Immunol. (2003) [Pubmed]
  32. Functional consequences of the binding of MHC class II-derived peptides to MHC class II. Feili-Hariri, M., Kao, H., Mietzner, T.A., Morel, P.A. Int. Immunol. (1996) [Pubmed]
  33. The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein peptide 103-116. Kjellén, P., Jansson, L., Vestberg, M., Andersson, A., Mattsson, R., Holmdahl, R. J. Neuroimmunol. (2001) [Pubmed]
  34. I-Ak polymorphisms define a functionally dominant region for the presentation of hen egg lysozyme peptides. Rosloniec, E.F., Vitez, L.J., Beck, B.N., Buerstedde, J.M., McKean, D.J., Landais, D., Benoist, C., Mathis, D., Freed, J.H. J. Immunol. (1989) [Pubmed]
  35. Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterning. Wendling, O., Ghyselinck, N.B., Chambon, P., Mark, M. Development (2001) [Pubmed]
  36. Multiple functional sites on a single Ia molecule defined using T cell clones and antibodies with chain-determined specificity. Frelinger, J.G., Shigeta, M., Infante, A.J., Nelson, P.A., Pierres, M., Fathman, C.G. J. Exp. Med. (1984) [Pubmed]
  37. Structure of murine Ia antigens. Two dimensional electrophoretic analyses and high pressure liquid chromatography tryptic peptide maps of products of the I-A and I-E subregions and of an associated invariant polypeptide. McMillan, M., Frelinger, J.A., Jones, P.P., Murphy, D.B., McDevitt, H.O., Hood, L. J. Exp. Med. (1981) [Pubmed]
  38. Biochemical characterization of Ia antigens. Characterization of a 22,000-dalton A delta d polypeptide expressed by I-Ad haplotype mice. McKean, D.J. J. Immunol. (1983) [Pubmed]
  39. Recombination and mutation of class II histocompatibility genes in wild mice. Wakeland, E.K., Darby, B.R. J. Immunol. (1983) [Pubmed]
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