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Gene Review

H2-M3  -  histocompatibility 2, M region locus 3

Mus musculus

Synonyms: H-2M3, Hmt, M3a, R4B2
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Disease relevance of H2-M3


High impact information on H2-M3


Chemical compound and disease context of H2-M3


Biological context of H2-M3


Anatomical context of H2-M3

  • Thus, the early H2-M3-restricted response temporally bridges the gap between innate and adaptive immune responses, subsequently affecting the function of both branches of the immune system [1].
  • The mouse MHC class I-b molecule H2-M3 has unique specificity for N-formyl peptides, derived from bacteria (and mitochondria), and is thus a pathogen-associated molecular pattern recognition receptor (PRR) [13].
  • Mta, the maternally transmitted antigen of mice, is a hydrophobic, N-formylated mitochondrial peptide, MTF, presented on the cell surface to cytotoxic T lymphocytes by a novel major histocompatibility complex class I molecule, encoded by H-2M3 [7].
  • We propose that Hmt encodes a class I histocompatibility antigen that acts as a restricting element for the Mtf gene product, thus meeting the requirements of T killer cell recognition [14].
  • This membrane orientation offers an explanation for the protection of the epitope from deformylases present in the bacterial cell and suggests an explanation for the ability of phagocytes to present H2-M3-restricted bacterial epitopes via a vacuolar TAP-independent mechanism [15].

Associations of H2-M3 with chemical compounds

  • When formylated D-alanine or D-methionine replaced the native methionine, these peptide derivatives did not show significant binding to M3a [16].
  • Additionally, the ability of M3a to discriminate between the optical forms of methionine and alanine demonstrates that this N-formyl pocket is stereospecific in its ability to bind peptide [16].
  • Substitutions with other hydrophobic amino acids such as N-formyl phenylalanine and N-formyl valine had no significant effect on the ability of these Mtf alpha analogues to sensitize target cells (M3a, Mtf beta) to M3a, Mtf alpha-specific CTL [16].
  • Listeria-encoded fMet peptide epitopes for H2-M3-restricted CTL have recently been identified [17].
  • Cross-recognition of N-formylmethionine peptides is a general characteristic of H2-M3-restricted CD8+ T cells [18].

Regulatory relationships of H2-M3

  • Tapasin enhances peptide-induced expression of H2-M3 molecules, but is not required for the retention of open conformers [19].

Other interactions of H2-M3

  • We have recently established a TCR transgenic mouse model (C10.4 TCRtrans+) in which the transgenic TCR was selected on the nonclassical MHC class Ib molecule H2-M3 in conjunction with a physiologically occurring peptide derived from the mitochondrial NADH-dehydrogenase subunit 1 gene (9-mer peptide) [20].
  • Thus, this report increases the number of MHC class Ib antigen-presenting molecules known for Salmonella antigens to three: Qa-1, HLA-E, and now H2-M3 [2].
  • However, unlike the classical class I genes, the Thy19.4 gene maps approximately 1 cm distal to the Tla region of the MHC, in the same region as the gene encoding the Hmt element of the maternally transmitted antigen [21].
  • These H2-M3-restricted T cells are cytolytic and produce interferon gamma [3].
  • Incubation of RMA-S cells with oligomycin, an inhibitor of mitochondrial ATPase, strongly increased lysis by cytotoxic T lymphocytes (CTL) specific for the class Ib antigen H2-M3, and lysis by Qa-1b-specific CTL was restored [22].


  1. Impaired response to Listeria in H2-M3-deficient mice reveals a nonredundant role of MHC class Ib-specific T cells in host defense. Xu, H., Chun, T., Choi, H.J., Wang, B., Wang, C.R. J. Exp. Med. (2006) [Pubmed]
  2. H2-M3 major histocompatibility complex class Ib-restricted CD8 T cells induced by Salmonella enterica serovar Typhimurium infection recognize proteins released by Salmonella serovar Typhimurium. Ugrinovic, S., Brooks, C.G., Robson, J., Blacklaws, B.A., Hormaeche, C.E., Robinson, J.H. Infect. Immun. (2005) [Pubmed]
  3. H2-M3-restricted T cells in bacterial infection: rapid primary but diminished memory responses. Kerksiek, K.M., Busch, D.H., Pilip, I.M., Allen, S.E., Pamer, E.G. J. Exp. Med. (1999) [Pubmed]
  4. Peptide affinity and concentration affect the sensitivity of M3-restricted CTLs induced in vitro. Byers, D.E., Lindahl, K.F. J. Immunol. (1999) [Pubmed]
  5. H2-M3, a full-service class Ib histocompatibility antigen. Lindahl, K.F., Byers, D.E., Dabhi, V.M., Hovik, R., Jones, E.P., Smith, G.P., Wang, C.R., Xiao, H., Yoshino, M. Annu. Rev. Immunol. (1997) [Pubmed]
  6. H-2M3 presents a Listeria monocytogenes peptide to cytotoxic T lymphocytes. Pamer, E.G., Wang, C.R., Flaherty, L., Lindahl, K.F., Bevan, M.J. Cell (1992) [Pubmed]
  7. H-2M3 encodes the MHC class I molecule presenting the maternally transmitted antigen of the mouse. Wang, C.R., Loveland, B.E., Lindahl, K.F. Cell (1991) [Pubmed]
  8. Positive selection of an H2-M3 restricted T cell receptor. Berg, R.E., Princiotta, M.F., Irion, S., Moticka, J.A., Dahl, K.R., Staerz, U.D. Immunity (1999) [Pubmed]
  9. Variable immunodominance hierarchies for H2-M3-restricted N-formyl peptides following bacterial infection. Kerksiek, K.M., Busch, D.H., Pamer, E.G. J. Immunol. (2001) [Pubmed]
  10. Specialized functions of MHC class I molecules. I. An N-formyl peptide receptor is required for construction of the class I antigen Mta. Shawar, S.M., Cook, R.G., Rodgers, J.R., Rich, R.R. J. Exp. Med. (1990) [Pubmed]
  11. Mitochondrial DNA segregation in hematopoietic lineages does not depend on MHC presentation of mitochondrially encoded peptides. Battersby, B.J., Redpath, M.E., Shoubridge, E.A. Hum. Mol. Genet. (2005) [Pubmed]
  12. The COI mitochondrial gene encodes a minor histocompatibility antigen presented by H2-M3. Morse, M.C., Bleau, G., Dabhi, V.M., Hétu, F., Drobetsky, E.A., Lindahl, K.F., Perreault, C. J. Immunol. (1996) [Pubmed]
  13. Hyperconservation of the N-formyl peptide binding site of M3: evidence that M3 is an old eutherian molecule with conserved recognition of a pathogen-associated molecular pattern. Doyle, C.K., Davis, B.K., Cook, R.G., Rich, R.R., Rodgers, J.R. J. Immunol. (2003) [Pubmed]
  14. Mta, the maternally transmitted antigen, is determined jointly by the chromosomal Hmt and the extrachromosomal Mtf genes. Lindahl, K.F., Hausmann, B., Robinson, P.J., Guénet, J.L., Wharton, D.C., Winking, H. J. Exp. Med. (1986) [Pubmed]
  15. Identification of an H2-M3-restricted Listeria epitope: implications for antigen presentation by M3. Lenz, L.L., Dere, B., Bevan, M.J. Immunity (1996) [Pubmed]
  16. Biochemical specificity of H-2M3a. Stereospecificity and space-filling requirements at position 1 maintain N-formyl peptide binding. Vyas, J.M., Shawar, S.M., Rodgers, J.R., Cook, R.G., Rich, R.R. J. Immunol. (1992) [Pubmed]
  17. CTL responses to H2-M3-restricted Listeria epitopes. Lenz, L.L., Bevan, M.J. Immunol. Rev. (1997) [Pubmed]
  18. Cross-recognition of N-formylmethionine peptides is a general characteristic of H2-M3-restricted CD8+ T cells. Ploss, A., Tran, A., Menet, E., Leiner, I., Pamer, E.G. Infect. Immun. (2005) [Pubmed]
  19. Tapasin enhances peptide-induced expression of H2-M3 molecules, but is not required for the retention of open conformers. Lybarger, L., Yu, Y.Y., Chun, T., Wang, C.R., Grandea, A.G., Van Kaer, L., Hansen, T.H. J. Immunol. (2001) [Pubmed]
  20. A physiological ligand of positive selection is seen with high specificity. Irion, S., Berg, R.E., Staerz, U.D. J. Immunol. (2000) [Pubmed]
  21. Analysis of a new class I gene mapping to the Hmt region of the mouse. Brorson, K.A., Richards, S., Hunt, S.W., Cheroutre, H., Lindahl, K.F., Hood, L. Immunogenetics (1989) [Pubmed]
  22. Increased class Ib antigen display on TAP-2 mutant cells by a mitochondrial function inhibitor. Hermel, E., Grigorenko, E., Aldrich, C.J. Cell. Immunol. (1997) [Pubmed]
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