Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Jul 1;174(1):213–218. doi: 10.1084/jem.174.1.213

Highly restricted expression of the thymus leukemia antigens on intestinal epithelial cells

PMCID: PMC2118879  PMID: 1711563

Abstract

The TL region of the major histocompatibility complex of the mouse contains dozens of tandemly arranged class I genes, including those encoding the thymus leukemia (TL) antigens. TL antigens have been thought to be expressed only on the surface of some T lineage cells, namely immature thymocytes of some mouse strains (TL+ strains), some leukemia cells, and activated T cells. While the function of TL antigens is unknown, recent studies have implicated the products of at least some TL region class I genes as molecules that present antigens to gamma/delta T cells. Since some gamma/delta T cells are known to be specifically associated with certain epithelial tissues, we have investigated the expression of some TL region class I genes in a variety of epithelium-containing tissues. Our results show that the TL antigen gene of C57BL/6 mice, T3b, and the TL antigen genes of BALB/c mice, T3d (previously T3c) and T18d (previously T13c), are highly expressed in the epithelium of the small intestine. In the case of T3b, we further show, using a T3 product-specific antibody, that its product is expressed on the surface of the columnar epithelial cells. In addition, we demonstrated that two other TL region class I genes of C57BL/6 origin, T9b and T21b, are also expressed nearly exclusively in intestinal epithelial cells. These results are consistent with the hypothesis that the products of these TL region class I genes are recognized by gamma/delta T cell receptors of intestinal intraepithelial lymphocytes, a subset of gamma/delta T cells that is localized in the intestinal epithelium and has a restricted V gamma repertoire. Finally, our study indicates that the relative levels of expression of the two homologous TL antigen genes, T3d and T18d, differ widely between the thymus and the intestine.

Full Text

The Full Text of this article is available as a PDF (798.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BOYSE E. A., OLD L. J., LUELL S. GENETIC DETERMINATION OF THE TL (THYMUSLEUKAEMIA) ANTIGEN IN THE MOUSE. Nature. 1964 Feb 22;201:779–779. doi: 10.1038/201779a0. [DOI] [PubMed] [Google Scholar]
  2. Bluestone J. A., Cron R. Q., Cotterman M., Houlden B. A., Matis L. A. Structure and specificity of T cell receptor gamma/delta on major histocompatibility complex antigen-specific CD3+, CD4-, CD8- T lymphocytes. J Exp Med. 1988 Nov 1;168(5):1899–1916. doi: 10.1084/jem.168.5.1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bonneville M., Ito K., Krecko E. G., Itohara S., Kappes D., Ishida I., Kanagawa O., Janeway C. A., Murphy D. B., Tonegawa S. Recognition of a self major histocompatibility complex TL region product by gamma delta T-cell receptors. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5928–5932. doi: 10.1073/pnas.86.15.5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonneville M., Itohara S., Krecko E. G., Mombaerts P., Ishida I., Katsuki M., Berns A., Farr A. G., Janeway C. A., Jr, Tonegawa S. Transgenic mice demonstrate that epithelial homing of gamma/delta T cells is determined by cell lineages independent of T cell receptor specificity. J Exp Med. 1990 Apr 1;171(4):1015–1026. doi: 10.1084/jem.171.4.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bonneville M., Janeway C. A., Jr, Ito K., Haser W., Ishida I., Nakanishi N., Tonegawa S. Intestinal intraepithelial lymphocytes are a distinct set of gamma delta T cells. Nature. 1988 Dec 1;336(6198):479–481. doi: 10.1038/336479a0. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Chorney M. J., Mashimo H., Bushkin Y., Nathenson S. G. Characterization of the thymus leukemia (TL) product encoded by the BALB/c T3c gene by DNA-mediated gene transfer. Comparison to the T13c product and BALB/c leukemia TL. J Immunol. 1989 Dec 1;143(11):3762–3768. [PubMed] [Google Scholar]
  8. Cook R. G., Landolfi N. F. Expression of the thymus leukemia antigen by activated peripheral T lymphocytes. J Exp Med. 1983 Sep 1;158(3):1012–1017. doi: 10.1084/jem.158.3.1012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cron R. Q., Koning F., Maloy W. L., Pardoll D., Coligan J. E., Bluestone J. A. Peripheral murine CD3+, CD4-, CD8- T lymphocytes express novel T cell receptor gamma delta structures. J Immunol. 1988 Aug 15;141(4):1074–1082. [PubMed] [Google Scholar]
  10. Ferrick D. A., Sydora B., Wallace V., Gemmell-Hori L., Kronenberg M., Mak T. W. Self-reactive gamma delta T lymphocytes: implications for T-cell ontogeny and reactivity. Immunol Rev. 1991 Apr;120:51–69. doi: 10.1111/j.1600-065x.1991.tb00587.x. [DOI] [PubMed] [Google Scholar]
  11. Fisher D. A., Hunt S. W., 3rd, Hood L. Structure of a gene encoding a murine thymus leukemia antigen, and organization of Tla genes in the BALB/c mouse. J Exp Med. 1985 Aug 1;162(2):528–545. doi: 10.1084/jem.162.2.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goodenow R. S., McMillan M., Nicolson M., Sher B. T., Eakle K., Davidson N., Hood L. Identification of the class I genes of the mouse major histocompatibility complex by DNA-mediated gene transfer. Nature. 1982 Nov 18;300(5889):231–237. doi: 10.1038/300231a0. [DOI] [PubMed] [Google Scholar]
  13. Hershberg R., Eghtesady P., Sydora B., Brorson K., Cheroutre H., Modlin R., Kronenberg M. Expression of the thymus leukemia antigen in mouse intestinal epithelium. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9727–9731. doi: 10.1073/pnas.87.24.9727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ito K., Van Kaer L., Bonneville M., Hsu S., Murphy D. B., Tonegawa S. Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell. 1990 Aug 10;62(3):549–561. doi: 10.1016/0092-8674(90)90019-b. [DOI] [PubMed] [Google Scholar]
  15. Janeway C. A., Jr Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):1–13. doi: 10.1101/sqb.1989.054.01.003. [DOI] [PubMed] [Google Scholar]
  16. Klein J., Benoist C., David C. S., Demant P., Lindahl K. F., Flaherty L., Flavell R. A., Hämmerling U., Hood L. E., Hunt S. W., 3rd Revised nomenclature of mouse H-2 genes. Immunogenetics. 1990;32(3):147–149. doi: 10.1007/BF02114967. [DOI] [PubMed] [Google Scholar]
  17. Koning F., Stingl G., Yokoyama W. M., Yamada H., Maloy W. L., Tschachler E., Shevach E. M., Coligan J. E. Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal Cell lines. Science. 1987 May 15;236(4803):834–837. doi: 10.1126/science.2883729. [DOI] [PubMed] [Google Scholar]
  18. Kuziel W. A., Takashima A., Bonyhadi M., Bergstresser P. R., Allison J. P., Tigelaar R. E., Tucker P. W. Regulation of T-cell receptor gamma-chain RNA expression in murine Thy-1+ dendritic epidermal cells. Nature. 1987 Jul 16;328(6127):263–266. doi: 10.1038/328263a0. [DOI] [PubMed] [Google Scholar]
  19. Michaelson J., Boyse E. A., Ciccia L., Flaherty L., Fleissner E., Garnick E., Hämmerling U., Lawrence M., Mauch P., Shen F. W. Biochemical genetics of TL antigens. Immunogenetics. 1986;24(2):103–114. doi: 10.1007/BF00373117. [DOI] [PubMed] [Google Scholar]
  20. OLD L. J., BOYSE E. A. ANTIGENIC PROPERTIES OF EXPERIMENTAL LEUKEMIAS. I. SEROLOGICAL STUDIES IN VITRO WITH SPONTANEOUS AND RADIATION-INDUCED LEUKEMIAS. J Natl Cancer Inst. 1963 Oct;31:977–995. [PubMed] [Google Scholar]
  21. Obata Y., Chen Y. T., Stockert E., Old L. J. Structural analysis of TL genes of the mouse. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5475–5479. doi: 10.1073/pnas.82.16.5475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Obata Y., Stockert E., Chen Y. T., Takahashi T., Old L. J. Influence of 5' flanking sequences on TL and H-2 expression in transfected L cells. Proc Natl Acad Sci U S A. 1988 May;85(10):3541–3545. doi: 10.1073/pnas.85.10.3541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Old L. J., Stockert E. Immunogenetics of cell surface antigens of mouse leukemia. Annu Rev Genet. 1977;11:127–160. doi: 10.1146/annurev.ge.11.120177.001015. [DOI] [PubMed] [Google Scholar]
  24. Pontarotti P. A., Mashimo H., Zeff R. A., Fisher D. A., Hood L., Mellor A., Flavell R. A., Nathenson S. G. 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. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1782–1786. doi: 10.1073/pnas.83.6.1782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stroynowski I. Molecules related to class-I major histocompatibility complex antigens. Annu Rev Immunol. 1990;8:501–530. doi: 10.1146/annurev.iy.08.040190.002441. [DOI] [PubMed] [Google Scholar]
  26. Takagaki Y., DeCloux A., Bonneville M., Tonegawa S. Diversity of gamma delta T-cell receptors on murine intestinal intra-epithelial lymphocytes. Nature. 1989 Jun 29;339(6227):712–714. doi: 10.1038/339712a0. [DOI] [PubMed] [Google Scholar]
  27. Tanaka K., Ozato K., Jay G., Parnes J. R., Ramanathan L., Seidman J. G., Chang K. S., Appella E. Control of H-2 antigen and beta 2-microglobulin gene expression in mouse trophoblast cell clones. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5597–5601. doi: 10.1073/pnas.80.18.5597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tonegawa S., Berns A., Bonneville M., Farr A., Ishida I., Ito K., Itohara S., Janeway C. A., Jr, Kanagawa O., Katsuki M. Diversity, development, ligands, and probable functions of gamma delta T cells. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):31–44. doi: 10.1101/sqb.1989.054.01.005. [DOI] [PubMed] [Google Scholar]
  29. Transy C., Nash S. R., David-Watine B., Cochet M., Hunt S. W., 3rd, Hood L. E., Kourilsky P. A low polymorphic mouse H-2 class I gene from the Tla complex is expressed in a broad variety of cell types. J Exp Med. 1987 Aug 1;166(2):341–361. doi: 10.1084/jem.166.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vidović D., Roglić M., McKune K., Guerder S., MacKay C., Dembić Z. Qa-1 restricted recognition of foreign antigen by a gamma delta T-cell hybridoma. Nature. 1989 Aug 24;340(6235):646–650. doi: 10.1038/340646a0. [DOI] [PubMed] [Google Scholar]
  31. Weiss E. H., Golden L., Fahrner K., Mellor A. L., Devlin J. J., Bullman H., Tiddens H., Bud H., Flavell R. A. Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse. Nature. 1984 Aug 23;310(5979):650–655. doi: 10.1038/310650a0. [DOI] [PubMed] [Google Scholar]
  32. Wolf P. R., Cook R. G. The TL region gene 37 encodes a Qa-1 antigen. J Exp Med. 1990 Dec 1;172(6):1795–1804. doi: 10.1084/jem.172.6.1795. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES