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Gene Review

H2-T18  -  histocompatibility 2, T region locus 18

Mus musculus

Synonyms: H-2T18, TL Ag, TLAg, Tla
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Disease relevance of H2-T18


High impact information on H2-T18

  • M3 is as divergent from classical, antigen-presenting H-2 molecules as from other class I genes of the Hmt and the Qa/Tla regions [5].
  • The H-2, Qa, and Tla genes of the murine major histocompatibility complex are related to each other by DNA sequence homology [6].
  • Linked to the murine MHC are genes encoding the class I-like Qa and Tla antigens, which are closely related structurally to H-2K, D and L, as they are also 45,000-Mr cell surface glycoproteins associated with beta 2-microglobulin [7].
  • A cDNA clone corresponding to a mRNA present at elevated levels in transformed fibroblasts encodes a Qa/Tla class I major histocompatibility complex (MHC) antigen [8].
  • Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice [9].

Biological context of H2-T18


Anatomical context of H2-T18

  • Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies [13].
  • A panel of peritoneal exudate cells (PEC) from mice bearing nonrecombinant and recombinant H-2-Tla haplotypes and their F1 hybrids was used as the source of target and inhibitor cells for direct lytic and competitive inhibition assays [14].
  • Mutant classical class I molecules substituted with TL Ag amino acids at these positions mimic the ability to interact with CD8alphaalpha and modulate lymphocyte function [15].
  • We conclude from these data that, in the cell membrane of thymocytes, virtually all the beta2m molecules are associated with H-2 and Tla, but not with Thy-1, and that on the cell surface of T or B lymphocytes, virtually all beta2m is associated with H-2 but not with Ia [16].
  • Antigens specified by the Tla locus are expressed on the surface of murine Langerhans cells [17].

Associations of H2-T18 with chemical compounds

  • Peanut agglutinin-positive thymocytes, peanut agglutinin-negative thymocytes, cortisone-resistant thymocytes, and unfractionated thymocytes were prepared from congeneic C57BL/6 Tla mice [18].
  • Three Tla region-specific probes have been generated from the BALB/c genomic cosmid clone C6 [19].
  • Serum from mice of a congenic strain being derived in our laboratory, which differs from B6 at two unlinked loci, Tla and nu, exhibited similar reactivity against the B6-H-2k LPS-stimulated lymphoblasts, implying that a competent T cell compartment is not necessary for generation of this reactivity [20].

Physical interactions of H2-T18

  • 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) [21].

Other interactions of H2-T18

  • Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene [22].
  • Northern (RNA) blot hybridizations, polymerase chain reaction studies, and cDNA cloning experiments demonstrate that EC lines transcribe genes allelic to the Tla region gene "37", Qa-2 region gene "Q7", and another, previously uncharacterized, class I-like gene [2].
  • Tests with recombinant inbred strains and with H-3 congenic strains show that, in addition to the Tla region, a gene linked to or identical with the beta 2-microglobulin-b-allele is required for the expression of Qa-11 as well [23].
  • 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 [24].
  • At least one new TL antigen is defined (TL.7), and at least one more Tla allele, bringing the total number of known Tla alleles to six [25].

Analytical, diagnostic and therapeutic context of H2-T18

  • Accordingly, we may have isolate genes encoding lymphoid differentiation antigens of the Tla complex as well as those encoding transplantation antigens among the 30 to 40 different genomic clones isolated from our sperm library [10].
  • Examination of this subset of Tla genes (T3b, T3c, and T13c) by restriction enzyme analysis and oligonucleotide hybridization studies confirmed that T3b is the allele of T3c and that T3c and T13c may have arisen by duplication [1].
  • Multiple species of TL mRNA were detected in TL+ cells by Northern blot analysis with pTL1, and different Tla haplotypes could be distinguished on the basis of characteristic patterns of TL mRNA [26].
  • Molecular relationships between beta2m and other cell surface antigens (H-2, Tla, Ia, and Thy-1) were studied with the double immunofluorescence method [16].
  • Cell surface forms of TL were detectable by immunoprecipitation on activated peripheral T cells from Tla haplotypes except Tla(b), in agreement with expression observed on thymocytes [27].


  1. Conservation and diversity in the class I genes of the major histocompatibility complex: sequence analysis of a Tlab gene and comparison with a Tlac gene. Pontarotti, P.A., Mashimo, H., Zeff, R.A., Fisher, D.A., Hood, L., Mellor, A., Flavell, R.A., Nathenson, S.G. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  2. Embryonal carcinoma cells express Qa and Tla class I genes of the major histocompatibility complex. Ostrand-Rosenberg, S., Nickerson, D.A., Clements, V.K., Garcia, E.P., Lamouse-Smith, E., Hood, L., Stroynowski, I. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  3. Demyelination induced by Theiler's virus: influence of the H-2 haplotype. Rodriguez, M., David, C.S. J. Immunol. (1985) [Pubmed]
  4. A gene(s) within the H-2D region determines the development of toxoplasmic encephalitis in mice. Suzuki, Y., Joh, K., Orellana, M.A., Conley, F.K., Remington, J.S. Immunology (1991) [Pubmed]
  5. 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]
  6. 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]
  7. Class I-like HLA genes map telomeric to the HLA-A2 locus in human cells. Orr, H.T., DeMars, R. Nature (1983) [Pubmed]
  8. Activation of a Qa/Tla class I major histocompatibility antigen gene is a general feature of oncogenesis in the mouse. Brickell, P.M., Latchman, D.S., Murphy, D., Willison, K., Rigby, P.W. Nature (1983) [Pubmed]
  9. Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice. Joyce, S., Negishi, I., Boesteanu, A., DeSilva, A.D., Sharma, P., Chorney, M.J., Loh, D.Y., Van Kaer, L. J. Exp. Med. (1996) [Pubmed]
  10. A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains. Steinmetz, M., Moore, K.W., Frelinger, J.G., Sher, B.T., Shen, F.W., Boyse, E.A., Hood, L. Cell (1981) [Pubmed]
  11. Submegabase clusters of unstable tandem repeats unique to the Tla region of mouse t haplotypes. Uehara, H., Ebersole, T., Bennett, D., Artzt, K. Genetics (1990) [Pubmed]
  12. Structure of a gene encoding a murine thymus leukemia antigen, and organization of Tla genes in the BALB/c mouse. Fisher, D.A., Hunt, S.W., Hood, L. J. Exp. Med. (1985) [Pubmed]
  13. Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies. Hämmerling, G.J., Hämmerling, U., Flaherty, L. J. Exp. Med. (1979) [Pubmed]
  14. Target determinants for F1 hybrid anti-parental H-2d cell-mediated lympholysis: self antigens controlled by the D end. Nakamura, I., Nakano, K., Cudkowicz, G. J. Immunol. (1983) [Pubmed]
  15. Molecular basis for the high affinity interaction between the thymic leukemia antigen and the CD8alphaalpha molecule. Attinger, A., Devine, L., Wang-Zhu, Y., Martin, D., Wang, J.H., Reinherz, E.L., Kronenberg, M., Cheroutre, H., Kavathas, P. J. Immunol. (2005) [Pubmed]
  16. Relationship between beta2-microglobulin and cell-surface alloantigens of the mouse. Geib, R., Poulik, M.D., Vitetta, E.S., Kearney, J.F., Klein, J. J. Immunol. (1976) [Pubmed]
  17. Antigens specified by the Tla locus are expressed on the surface of murine Langerhans cells. Rowden, G., Misra, B., Higley, H., Howard, R. J. Invest. Dermatol. (1983) [Pubmed]
  18. Changes in surface antigens of immature thymocytes under the influence of T-cell growth factor and thymic factors. Chen, S.S., Tung, J.S., Gillis, S., Good, R.A., Hadden, J.W. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  19. Structural analysis of TL genes of the mouse. Obata, Y., Chen, Y.T., Stockert, E., Old, L.J. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  20. Allogeneic reactivity in normal mouse serum. Lynes, M.A., Flaherty, L., Michaelson, J., Collins, J.J., Rinchik, E.M. J. Immunogenet. (1984) [Pubmed]
  21. H-2 haplotypes, genes and antigens: second listing. II. The H-2 complex. Klein, J., Figueroa, F., David, C.S. Immunogenetics (1983) [Pubmed]
  22. Proximity of the Mep-1 gene to H-2D on chromosome 17 in mice. Reckelhoff, J.F., Bond, J.S., Beynon, R.J., Savarirayan, S., David, C.S. Immunogenetics (1985) [Pubmed]
  23. A new Tla region antigen Qa-11, similar to Qa-2 and associated with B-type beta 2-microglobulin. van de Meugheuvel, W., van Seventer, G., Demant, P. J. Immunol. (1985) [Pubmed]
  24. 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]
  25. Further polymorphism of the Tla locus defined by monoclonal TL antibodies. Shen, F.W., Chorney, M.J., Boyse, E.A. Immunogenetics (1982) [Pubmed]
  26. Thymus-leukemia (TL) antigens of the mouse. Analysis of TL mRNA and TL cDNA TL+ and TL- strains. Chen, Y.T., Obata, Y., Stockert, E., Old, L.J. J. Exp. Med. (1985) [Pubmed]
  27. Regulation of expression of TL genes of the mouse Mhc. Dolby, N., Mehta, V., Cook, R.G. Immunogenetics (1990) [Pubmed]
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