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Gene Review

H2  -  histocompatibility-2, MHC

Mus musculus

Synonyms: H-2, MHC-II
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Disease relevance of H2


Psychiatry related information on H2

  • This finding is most readily accommodated within the altered self concept (postulating that T cells are specific for virus-modified self structures) but cannot exclude the possibility of a physiological interaction mechanism being responsible for the apparent H-2 restriction of virus-specific cytotoxic T cells [6].

High impact information on H2

  • The H-2 genes encode ubiquitously expressed transplantation antigens that serve as recognition structures for cytotoxic T cells [7].
  • A panel of target cells was obtained by the double transfection and expression of a retrovirus gene and a foreign H-2 gene in recipient mouse fibroblasts [8].
  • They display enhancer-like activity in cells that express H-2 genes, but show some tissue specificity in that they function very poorly in undifferentiated embryonal carcinoma cells in which H-2 genes are not expressed [9].
  • On genomic DNA blots, the restriction fragments containing H-2-related sequences were highly variable among different inbred strains of mice, whereas they were very similar among different t haplotypes even when the t haplotypes carried serologically different H-2 haplotypes [10].
  • Naturally occurring t haplotypes suppress recombination over a region of mouse chromosome 17 that includes the H-2 complex [11].

Chemical compound and disease context of H2


Biological context of H2


Anatomical context of H2

  • In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact [21].
  • Transformation of murine NIH3T3 fibroblasts with retroviral vectors carrying the mos, myc and the Ha-ras oncogene, respectively, was associated with a strong reduction of H2 antigen expression in the cell membrane [22].
  • The K and D regions of the H-2 gene complex are highly polymorphic and control cell-surface structures involved in the H-2 restriction of cytotoxic T lymphocytes [23].
  • Comparison of H-2 antigens immunoprecipitated from normal spleen cells and from thioglycollate-induced adherent peritoneal exudate cells cultured in the presence or absence of supernatant fluids from concanavalin A-stimulated spleen cells revealed that H-2K' was not expressed on the adherent peritoneal cells [24].
  • V beta 3+ T cells are eliminated in Mls-2a mice carrying some, but not all, H-2 types [25].

Associations of H2 with chemical compounds

  • Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors [21].
  • Glyoxalase I polymorphism in the mouse: a new genetic marker linked to H-2 [17].
  • Lethal deletion of the complement component C4 and steroid 21-hydroxylase genes in the mouse H-2 class III region, caused by meiotic recombination [19].
  • We have continued our investigations of line lung carcinoma cells to understand the molecular basis of decreased expression of class I H-2 Ag and class I Ag induction with DMSO [26].
  • Sgp-1b, which appeared in most of the H-2 types tested, corresponds with low serum gp70 output in B10 congenic lines and F1 hybrid offspring of B10 and NZB crosses and with increased gp70 production after lipopolysaccharide (LPS) stimulation [27].

Physical interactions of H2

  • The results indicated that murine Bf was controlled by a single codominant locus located close to the H-2 complex because no mouse showing recombination between Bf locus and S locus was found [28].
  • We include into the H-2 complex the cluster of Qa and Tla loci, which we consider as class I loci (Klein et al. 1983) [29].
  • The most straightforward interpretation of the results presented here is that these t haplotypes carry an H-2 complex located between the centromere and tufted locus [30].
  • Chromosome 17 of the mouse carries the H-2 complex and the T/t complex [31].
  • Linkage studies showed that both of the major NZB and NZW genes are loosely linked to the H-2 complex but not to either the Mup-1 or coat color gene loci examined [32].

Regulatory relationships of H2

  • First, a profound inhibition of primary PFC responses occurs when foreign H-2 antigens are expressed on Thy-1 incompatible donor cells [33].
  • Our results demonstrate that the Ity gene may modulate the antibody responses to the foreign antigen but that the major genetic influence is exerted by H-2 genes, which control the capacity of mice to respond to the antigen expressed by recombinant attenuated Salmonella cells [34].
  • These experiments suggest that alloantisera to the H-2 complex express at least part of their inhibitory properties by blocking the Fc receptor on B cells, and the data support the concept that certain Ia antigens and the Fc receptor are identical or closely associated [35].
  • These findings suggest the possibility that orexin A may activate H1 and H2 receptors in the supraspinal levels through the release of histamine from neurons, which might attenuate the antinociceptive effects of orexin A [36].

Other interactions of H2

  • The finding that the D region controls H-2L and H-2M, as well as H-2D, molecules suggests that the system of H-2 antigens is more complicated [23].
  • In three such crosses, with 5* offspring, C3 segregated with H-2 in 46 instances, corresponding to a recombination frequency of approximately equal to 0.12 [20].
  • Control of H-2 class I and beta 2-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels [37].
  • Evidence for placing the Neu-1 locus within the mouse H-2 complex [38].
  • A classical breeding analysis of the complete t haplotypes, tw5 and t12, utilizing the newly induced markers, reveals two inversions in t chromatin: one involving T and qk, and one involving tf and the H-2 complex [39].

Analytical, diagnostic and therapeutic context of H2

  • A gene mapping between the S and D regions of the H-2 complex influences resistance to Trichinella spiralis infections of mice [40].
  • In L cells, these genes direct the synthesis of hybrid H-2 proteins and by using monoclonal antibodies of defined specificities, we have mapped classically defined serological specificities to structurally defined domains of the transplantation antigen protein [41].
  • Sequence analysis of mouse H-2 cDNA clones has suggested the existence of an unusual class of H-2 (class I)-related antigens that, unlike the classical membrane-associated molecules, retains only the extracellular portion and is likely to be secreted [42].
  • Qa-1-specific, H-2-unrestricted cytotoxic T lymphocytes (CTLs) generated from reciprocally immunized B10.BR (H-2k, Qa-1a) and CBA (H-2k, Qa-1b) mice, and immunoprecipitation of cell surface Qa-1 were used to examined Qa-1 region determinant expression by H-2r and H-2f mice [43].
  • We have found the definitive location of the H-2 complex by the use of in situ hybridization [31].


  1. Genes in mice that affect susceptibility to cortisone-induced cleft palate are closely linked to Ir genes on chromosomes 2 and 17. Gasser, D.L., Mele, L., Lees, D.D., Goldman, A.S. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  2. The L1210 leukemia cell bears a B lymphocyte specific, non-H-2 linked alloantigen. Freund, J.G., Ahmed, A., Budd, R.E., Dorf, M.E., Sell, K.W., Vannier, W.E., Humphreys, R.E. J. Immunol. (1976) [Pubmed]
  3. Genetic contributions of nonautoimmune SWR mice toward lupus nephritis. Xie, S., Chang, S., Yang, P., Jacob, C., Kaliyaperumal, A., Datta, S.K., Mohan, C. J. Immunol. (2001) [Pubmed]
  4. New revelations in susceptibility to autoimmune thyroiditis by the use of H2 and HLA class II transgenic models. Kong, Y.C., David, C.S. Int. Rev. Immunol. (2000) [Pubmed]
  5. Absence of significant H-2 and beta 2-microglobulin mRNA expression by mouse embryonal carcinoma cells. Morello, D., Daniel, F., Baldacci, P., Cayre, Y., Gachelin, G., Kourilsky, P. Nature (1982) [Pubmed]
  6. H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. The H-2K structure involved is coded by a single cistron defined by H-2Kb mutant mice. Zinkernagel, R.M. J. Exp. Med. (1976) [Pubmed]
  7. A single gene encodes soluble and membrane-bound forms of the major histocompatibility Qa-2 antigen: anchoring of the product by a phospholipid tail. Stroynowski, I., Soloski, M., Low, M.G., Hood, L. Cell (1987) [Pubmed]
  8. Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Plata, F., Langlade-Demoyen, P., Abastado, J.P., Berbar, T., Kourilsky, P. Cell (1987) [Pubmed]
  9. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Kimura, A., Israël, A., Le Bail, O., Kourilsky, P. Cell (1986) [Pubmed]
  10. Genetic structure and origin of t haplotypes of mice, analyzed with H-2 cDNA probes. Shin, H.S., Stavnezer, J., Artzt, K., Bennett, D. Cell (1982) [Pubmed]
  11. Genomic analysis of the H-2 complex region associated with mouse t haplotypes. Silver, L.M. Cell (1982) [Pubmed]
  12. Acute autoimmune encephalomyelitis in mice. II. Susceptibility is controlled by the combination of H-2 and histamine sensitization genes. Linthicum, D.S., Frelinger, J.A. J. Exp. Med. (1982) [Pubmed]
  13. Functional analysis of the mouse H-2Kb gene promoter in embryonal carcinoma cells. Daniel-Vedele, F., Israel, A., Benicourt, C., Kourilsky, P. Immunogenetics (1985) [Pubmed]
  14. H-2 histocompatibility region influences the inhibition of arachidonic acid cascade by dexamethasone and phenytoin in mouse embryonic palates. Gupta, C., Katsumata, M., Goldman, A.S. J. Craniofac. Genet. Dev. Biol. (1985) [Pubmed]
  15. Association of Bordetella pertussis-induced hypersensitivity to serotonin with the H-2 gene complex. Teuscher, C. J. Immunogenet. (1986) [Pubmed]
  16. Susceptibility to experimental interstitial lung disease is modified by immune- and non-immune-related genes. Rossi, G.A., Szapiel, S., Ferrans, V.J., Crystal, R.G. Am. Rev. Respir. Dis. (1987) [Pubmed]
  17. Glyoxalase I polymorphism in the mouse: a new genetic marker linked to H-2. Meo, T., Douglas, T., Rijnbeek, A.M. Science (1977) [Pubmed]
  18. Dendritic cell maturation overrules H-2D-mediated natural killer T (NKT) cell inhibition: critical role for B7 in CD1d-dependent NKT cell interferon gamma production. Ikarashi, Y., Mikami, R., Bendelac, A., Terme, M., Chaput, N., Terada, M., Tursz, T., Angevin, E., Lemonnier, F.A., Wakasugi, H., Zitvogel, L. J. Exp. Med. (2001) [Pubmed]
  19. Lethal deletion of the complement component C4 and steroid 21-hydroxylase genes in the mouse H-2 class III region, caused by meiotic recombination. Shiroishi, T., Sagai, T., Natsuume-Sakai, S., Moriwaki, K. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  20. Murine complement component 3: genetic variation and linkage to H-2. Da Silva, F.P., Hoecker, G.F., Day, N.K., Vienne, K., Rubinstein, P. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  21. Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors. Dai, H., Kaneko, K., Kato, H., Fujii, S., Jing, Y., Xu, A., Sakurai, E., Kato, M., Okamura, N., Kuramasu, A., Yanai, K. Neurosci. Res. (2007) [Pubmed]
  22. Post-transcriptional downregulation of MHC class I expression in oncogene-transformed cells is reverted by IFN-gamma and TNF-alpha. Seliger, B., Pfizenmaier, K. J. Immunogenet. (1989) [Pubmed]
  23. Further molecular complexities of H-2 K- and D-region antigens. Démant, P., Iványi, D. Nature (1981) [Pubmed]
  24. Identification of a second class I antigen controlled by the K end of the H-2 complex and its selective cellular expression. Tryphonas, M., King, D.P., Jones, P.P. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  25. Evidence that Mls-2 antigens which delete V beta 3+ T cells are controlled by multiple genes. Pullen, A.M., Marrack, P., Kappler, J.W. J. Immunol. (1989) [Pubmed]
  26. Molecular analysis of deficient class I H-2 antigen expression by mouse lung carcinoma cells. Bahler, D.W., Cerosaletti, K.M., Lord, E.M., Frelinger, J.G. J. Immunol. (1988) [Pubmed]
  27. H-2-linked regulation of serum gp70 production in mice. Maruyama, N., Lindstrom, C.O. Immunogenetics (1983) [Pubmed]
  28. Structural polymorphism of murine factor B controlled by a locus closely linked to the H-2 complex and demonstration of multiple alleles. Natsuume-Sakai, S., Moriwaki, K., Migita, S., Sudo, K., Suzuki, K., Lu, D.Y., Wang, C., Takahashi, M. Immunogenetics (1983) [Pubmed]
  29. H-2 haplotypes, genes and antigens: second listing. II. The H-2 complex. Klein, J., Figueroa, F., David, C.S. Immunogenetics (1983) [Pubmed]
  30. Recombination between two mouse t haplotypes (tw12tf and tLub-1): mapping of the H-2 complex relative to centromere and tufted (tf) locus. Pla, M., Condamine, H. Immunogenetics (1984) [Pubmed]
  31. Definitive chromosomal location of the H-2 complex by in situ hybridization to pachytene chromosomes. Lader, E., Clark, B.T., Jhanwar, S.C., Chaganti, R.S., Bennett, D. Immunogenetics (1985) [Pubmed]
  32. Genetic studies of autoimmunity in New Zealand mice. IV. Contribution of NZB and NZW genes to the spontaneous occurrence of retroviral gp70 immune complexes in (NZB X NZW)F1 hybrid and the correlation to renal disease. Maruyama, N., Furukawa, F., Nakai, Y., Sasaki, Y., Ohta, K., Ozaki, S., Hirose, S., Shirai, T. J. Immunol. (1983) [Pubmed]
  33. Modulation of Thy-1 alloantibody responses: donor cell-associated H-2 inhibition and augmentation without recipient Ir gene control. Clark, E.A., Lake, P., Favila-Castillo, L. J. Immunol. (1981) [Pubmed]
  34. Genetic control of antibody responses induced against an antigen delivered by recombinant attenuated Salmonella typhimurium. Fayolle, C., O'Callaghan, D., Martineau, P., Charbit, A., Clément, J.M., Hofnung, M., Leclerc, C. Infect. Immun. (1994) [Pubmed]
  35. Inhibition of in vitro immune responses by antisera to H-2 or Ir gene products. Tyan, M.L. Proc. Soc. Exp. Biol. Med. (1975) [Pubmed]
  36. Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice. Mobarakeh, J.I., Takahashi, K., Sakurada, S., Nishino, S., Watanabe, H., Kato, M., Naghdi, N., Yanai, K. Pain (2005) [Pubmed]
  37. Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level. Wilson, L.D., Flyer, D.C., Faller, D.V. Mol. Cell. Biol. (1987) [Pubmed]
  38. Evidence for placing the Neu-1 locus within the mouse H-2 complex. Figueroa, F., Klein, D., Tewarson, S., Klein, J. J. Immunol. (1982) [Pubmed]
  39. Genetic analysis of mouse t haplotypes using mutations induced by ethylnitrosourea mutagenesis: the order of T and qk is inverted in t mutants. Justice, M.J., Bode, V.C. Genetics (1988) [Pubmed]
  40. A gene mapping between the S and D regions of the H-2 complex influences resistance to Trichinella spiralis infections of mice. Wassom, D.L., Brooks, B.O., Babish, J.G., David, C.S. J. Immunogenet. (1983) [Pubmed]
  41. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Evans, G.A., Margulies, D.H., Shykind, B., Seidman, J.G., Ozato, K. Nature (1982) [Pubmed]
  42. Tissue-specific expression of an unusual H-2 (class I)-related gene. Cosman, D., Kress, M., Khoury, G., Jay, G. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  43. Qa-1-associated antigens. IV. Evidence for additional Qa-1 polymorphism defined biochemically and by cytotoxic T lymphocyte recognition. Nell, L.J., Cook, R.G., Rich, R.R. Transplantation (1982) [Pubmed]
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