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Gene Review

H2-Ab1  -  histocompatibility 2, class II antigen A,...

Mus musculus

Synonyms: A beta, AI845868, Abeta, H-2 class II histocompatibility antigen, A beta chain, H-2 class II histocompatibility antigen, A-D beta chain, ...
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Disease relevance of H2-Ab1


Psychiatry related information on H2-Ab1

  • It has been demonstrated that immunization of transgenic mouse models of Alzheimer's disease (AD) with amyloid-beta(1-42) peptide (Abeta(1-42)) results in prevention of Abeta plaque formation and amelioration of established plaques in the brain [6].
  • We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden [7].
  • We hypothesize that impaired synaptic plasticity and associated memory dysfunction during early stage Alzheimer's disease and severe cellular degeneration and dementia during end stage could be caused by the biphasic impact of Abeta-derived diffusible ligands acting upon particular neural signal transduction pathways [8].
  • Finally, mcip1/2-null mice displayed a neurologic phenotype that was similar to calcineurin Abeta-null mice, such as increased locomotor activity and impaired working memory [9].
  • The serologic lesion of the I-A mutant mouse strain, bm12, was investigated with the use of monoclonal anti-Iab antibodies and anti-idiotypic (Id) reagents produced against these antibodies [10].

High impact information on H2-Ab1

  • Mixed isotype (E alpha A beta and A alpha E beta) dimers are not found on Ia+ hematopoietic cells, although some pairs (e.g., E alpha A beta d) reach the membrane of transfected cells expressing only the two relevant class II genes [11].
  • Transgenic mice expressing both chains of the I-A gene showed progressive atrophy of the islets of Langerhans, whereas mice expressing interferon-gamma suffered an inflammatory destruction of the islets [12].
  • RNA analysis revealed a requirement for greater A beta, and particularly A alpha transcript levels in haplotype-mismatched vs. haplotype-matched transfectants with similar levels of membrane Ia [13].
  • In this report we present evidence that A beta 2 is transcribed in spleen and in a cultured B cell hybridoma [14].
  • The class II genes in the I region of the murine major histocompatibility complex encode the alpha and beta chains of the two known la antigens, I-A and I-E [14].

Chemical compound and disease context of H2-Ab1


Biological context of H2-Ab1


Anatomical context of H2-Ab1

  • CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw) [23].
  • Helper effect could be obtained only toward B cell sources that shared the H-2K and I-A antigens with the hybridoma cells [24].
  • IFN-gamma increases the surface expression of class II molecules in a murine B cell line without inducing detectable changes in either I-A or I-A mRNA levels [25].
  • Based on numbers of L. monocytogenes organisms in spleens, beta 2m -/- mutants suffered more dramatically from primary and secondary infection than A beta -/- mice [1].
  • Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB+/+ mouse embryonic fibroblasts (MEFs), but deficient in RB-/- MEFs [26].

Associations of H2-Ab1 with chemical compounds


Physical interactions of H2-Ab1

  • Moreover, major histocompatibility complex class II-deficient I-A-beta-/- mice were capable of mounting a substantial response to secondary infection, manifest by a 95% reduction in oocyst output compared with primary infection [29].
  • Studies on cell lines transfected with MHC class II genes have revealed important limitations on the assembly of haplotype-mismatched A alpha/A beta complexes [30].
  • The DNA minigene-induced anti-Abeta antibodies bound to Abeta plaques in brain tissue from an Alzheimer's disease patient demonstrating functional activity of the antibodies and the potential for therapeutic efficacy [31].
  • The molecular mass of the Abeta binding protein was estimated to be 49kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [32].

Regulatory relationships of H2-Ab1

  • Role of Na+/H+ exchange by interferon-gamma in enhanced expression of JE and I-A beta genes [33].
  • Production of IL-6 by human myoblasts stimulated with Abeta: relevance in the pathogenesis of IBM [3].
  • Macrophage colony-stimulating factor (M-CSF) inhibits the decrease in the amount of rRNA and IA beta mRNA in cultured epidermal Langerhans cells of the mouse [34].
  • We conclude that I-A beta gene expression is repressed by PU.1 binding to the PU box domain [35].
  • In particular, as shown in mice with the recombinant H-2 haplotype and in class II mutant bm12 mice, the I-A heterodimer controls the recognition of the immunodominant 40-kDa antigen [36].

Other interactions of H2-Ab1

  • We show here that the E beta b gene is identical to the non-allelic A beta bm12 DNA sequence in the mutated region and suggest, therefore, that the E beta b gene was the donor sequence for this intergenic transfer of genetic information [22].
  • The I region of the C57BL/10 mouse: characterization and physical linkage to H-2K of an SB beta-like class II pseudogene, psi A beta 3 [37].
  • Surface expression of MHC class I (Kb, Db) and class II (I-Ab) molecules by B16 cells was low, but strikingly up-regulated by IFN-gamma [38].
  • CONCLUSIONS: Cultured muscle cells increase the constitutive production of IL-6 in response to local deposition of Abeta in sporadic IBM [3].
  • Genetic diversity of class II genes in wild mice: definition of five evolutionary groups by RFLP analysis of A alpha and A beta [39].

Analytical, diagnostic and therapeutic context of H2-Ab1


  1. Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection. Ladel, C.H., Flesch, I.E., Arnoldi, J., Kaufmann, S.H. J. Immunol. (1994) [Pubmed]
  2. 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]
  3. Production of IL-6 by human myoblasts stimulated with Abeta: relevance in the pathogenesis of IBM. Baron, P., Galimberti, D., Meda, L., Scarpini, E., Conti, G., Cogiamanian, F., Scarlato, G. Neurology (2001) [Pubmed]
  4. Immune response to Mycobacterium bovis bacille Calmette Guérin infection in major histocompatibility complex class I- and II-deficient knock-out mice: contribution of CD4 and CD8 T cells to acquired resistance. Ladel, C.H., Daugelat, S., Kaufmann, S.H. Eur. J. Immunol. (1995) [Pubmed]
  5. Alpha-MSH peptides inhibit production of nitric oxide and tumor necrosis factor-alpha by microglial cells activated with beta-amyloid and interferon gamma. Galimberti, D., Baron, P., Meda, L., Prat, E., Scarpini, E., Delgado, R., Catania, A., Lipton, J.M., Scarlato, G. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  6. Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer's beta-amyloid(1-42). Town, T., Vendrame, M., Patel, A., Poetter, D., DelleDonne, A., Mori, T., Smeed, R., Crawford, F., Klein, T., Tan, J., Mullan, M. J. Neuroimmunol. (2002) [Pubmed]
  7. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Dodart, J.C., Bales, K.R., Gannon, K.S., Greene, S.J., DeMattos, R.B., Mathis, C., DeLong, C.A., Wu, S., Wu, X., Holtzman, D.M., Paul, S.M. Nat. Neurosci. (2002) [Pubmed]
  8. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Lambert, M.P., Barlow, A.K., Chromy, B.A., Edwards, C., Freed, R., Liosatos, M., Morgan, T.E., Rozovsky, I., Trommer, B., Viola, K.L., Wals, P., Zhang, C., Finch, C.E., Krafft, G.A., Klein, W.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Modulatory calcineurin-interacting proteins 1 and 2 function as calcineurin facilitators in vivo. Sanna, B., Brandt, E.B., Kaiser, R.A., Pfluger, P., Witt, S.A., Kimball, T.R., van Rooij, E., De Windt, L.J., Rothenberg, M.E., Tschop, M.H., Benoit, S.C., Molkentin, J.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. Idiotypic and fluorometric analysis of the antibodies that distinguish the lesion of the I-A mutant B6.C-H-2bm12. Melino, M.R., Epstein, S.L., Sachs, D.H., Hansen, T.H. J. Immunol. (1983) [Pubmed]
  11. Intracellular competition for component chains determines class II MHC cell surface phenotype. Sant, A.J., Germain, R.N. Cell (1989) [Pubmed]
  12. Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma. Sarvetnick, N., Liggitt, D., Pitts, S.L., Hansen, S.E., Stewart, T.A. Cell (1988) [Pubmed]
  13. Influence of allelic polymorphism on the assembly and surface expression of class II MHC (Ia) molecules. Germain, R.N., Bentley, D.M., Quill, H. Cell (1985) [Pubmed]
  14. Multiple mechanisms regulate the expression of murine immune response genes. Wake, C.T., Flavell, R.A. Cell (1985) [Pubmed]
  15. Amyloid-beta peptide fragments p3 and p4 induce pro-inflammatory cytokine and chemokine production in vitro and in vivo. Szczepanik, A.M., Rampe, D., Ringheim, G.E. J. Neurochem. (2001) [Pubmed]
  16. Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears beta-amyloid in a mouse model of Alzheimer disease. Frenkel, D., Maron, R., Burt, D.S., Weiner, H.L. J. Clin. Invest. (2005) [Pubmed]
  17. Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Barger, S.W., Hörster, D., Furukawa, K., Goodman, Y., Krieglstein, J., Mattson, M.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  18. Assignment of antigenic determinants to separated I-A kappa chains. Kupinski, J.M., Plunkett, M.L., Freed, J.H. J. Immunol. (1983) [Pubmed]
  19. Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. Ikehara, S., Kawamura, M., Takao, F., Inaba, M., Yasumizu, R., Than, S., Hisha, H., Sugiura, K., Koide, Y., Yoshida, T.O. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  20. 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]
  21. 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]
  22. The nucleotide sequence of the murine I-E beta b immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex. Widera, G., Flavell, R.A. EMBO J. (1984) [Pubmed]
  23. Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation. Tan, J., Town, T., Paris, D., Mori, T., Suo, Z., Crawford, F., Mattson, M.P., Flavell, R.A., Mullan, M. Science (1999) [Pubmed]
  24. H-2-restricted helper factor secreted by clone hybridoma cells. Lonai, P., Puri, J., Bitton, S., Ben-Neriah, Y., Givol, D., Hämmerling, G.J. J. Exp. Med. (1981) [Pubmed]
  25. Translational control of MHC class II I-A molecules by IFN-gamma. Goñalons, E., Barrachina, M., García-Sanz, J.A., Celada, A. J. Immunol. (1998) [Pubmed]
  26. pRB is required for interferon-gamma-induction of the MHC class II abeta gene. Zhu, X., Pattenden, S., Bremner, R. Oncogene (1999) [Pubmed]
  27. Detection of CML determinants associated with H-2 controlled E beta and E alpha chains. Juretić, A., Nagy, Z.A., Klein, J. Nature (1981) [Pubmed]
  28. Interferon-gamma activates multiple pathways to regulate the expression of the genes for major histocompatibility class II I-A beta, tumor necrosis factor and complement component C3 in mouse macrophages. Celada, A., Klemsz, M.J., Maki, R.A. Eur. J. Immunol. (1989) [Pubmed]
  29. Genetic analysis of the essential components of the immunoprotective response to infection with Eimeria vermiformis. Smith, A.L., Hayday, A.C. Int. J. Parasitol. (1998) [Pubmed]
  30. 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]
  31. Generation and characterization of the humoral immune response to DNA immunization with a chimeric beta-amyloid-interleukin-4 minigene. Ghochikyan, A., Vasilevko, V., Petrushina, I., Movsesyan, N., Babikyan, D., Tian, W., Sadzikava, N., Ross, T.M., Head, E., Cribbs, D.H., Agadjanyan, M.G. Eur. J. Immunol. (2003) [Pubmed]
  32. Characterization and purification of a protein binding to the cis-acting element for brain-specific exon 1 of the mouse aromatase gene. Honda, S.I., Matsumoto, T., Harada, N. J. Steroid Biochem. Mol. Biol. (2001) [Pubmed]
  33. Role of Na+/H+ exchange by interferon-gamma in enhanced expression of JE and I-A beta genes. Prpic, V., Yu, S.F., Figueiredo, F., Hollenbach, P.W., Gawdi, G., Herman, B., Uhing, R.J., Adams, D.O. Science (1989) [Pubmed]
  34. Macrophage colony-stimulating factor (M-CSF) inhibits the decrease in the amount of rRNA and IA beta mRNA in cultured epidermal Langerhans cells of the mouse. Koyama, Y., Marunouchi, T. J. Dermatol. (1996) [Pubmed]
  35. Repression of I-A beta gene expression by the transcription factor PU.1. Borràs, F.E., Lloberas, J., Maki, R.A., Celada, A. J. Biol. Chem. (1995) [Pubmed]
  36. Influence of genes from the major histocompatibility complex on the antibody repertoire against culture filtrate antigens in mice infected with live Mycobacterium bovis BCG. Huygen, K., Drowart, A., Harboe, M., ten Berg, R., Cogniaux, J., Van Vooren, J.P. Infect. Immun. (1993) [Pubmed]
  37. The I region of the C57BL/10 mouse: characterization and physical linkage to H-2K of an SB beta-like class II pseudogene, psi A beta 3. Widera, G., Flavell, R.A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  38. T cell-mediated, IFN-gamma-facilitated rejection of murine B16 melanomas. Böhm, W., Thoma, S., Leithäuser, F., Möller, P., Schirmbeck, R., Reimann, J. J. Immunol. (1998) [Pubmed]
  39. Genetic diversity of class II genes in wild mice: definition of five evolutionary groups by RFLP analysis of A alpha and A beta. Wakeland, E.K., McIndoe, R.A., McConnell, T.J. Curr. Top. Microbiol. Immunol. (1986) [Pubmed]
  40. Localization of a critical restriction site on the I-A beta chain that determines susceptibility to collagen-induced arthritis in mice. Holmdahl, R., Karlsson, M., Andersson, M.E., Rask, L., Andersson, L. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  41. Locally derived cytokines and upregulation of MHC class II genes in allografts. Kittur, D.S., Wilasrusmee, C., Han, W.F., Xu, R., Burdick, J.F., Adler, W. J. Heart Lung Transplant. (2002) [Pubmed]
  42. Comparative sequence analysis of cDNA clones encoding I-A molecules of the CH12 B cell lymphoma: nucleotide differences do not account for their "defective" function in B cell stimulation. Sharma, S., King, L.B., Corley, R.B., Maki, R. Immunol. Invest. (1987) [Pubmed]
  43. Post-thymic selection of peripheral CD4+ T-lymphocytes on class II major histocompatibility antigen-bearing cells. Shen, X., König, R. Cell. Mol. Biol. (Noisy-le-grand) (2001) [Pubmed]
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