Abstract
Cloned H-Y-specific murine cytotoxic T lymphocytes, which alter antigen specificity in vitro ("aging"), simultaneously exhibit changes in the T-cell antigen receptor beta-chain rearrangements and respective mRNAs expressed. beta-chain cDNA clones were isolated from a library prepared from mRNA of aged killer T cells. The sequence of the beta-chain variable region element (VAK) was found to be identical with germ-line DNA. Four bases at the beta-chain diversity-joining region (D beta--J beta) junction cannot be explained by known germ-line D beta and J beta elements. These results illustrate that in T-cell clones altered antigen specificity correlates with a switch in productive beta-chain rearrangements of the T-cell receptor. When tested for its expression under physiological conditions, significant levels of VAK mRNA were found in normal lymphocyte populations.
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- Acuto O., Campen T. J., Royer H. D., Hussey R. E., Poole C. B., Reinherz E. L. Molecular analysis of T cell receptor (Ti) variable region (V) gene expression. Evidence that a single Ti beta V gene family can be used in formation of V domains on phenotypically and functionally diverse T cell populations. J Exp Med. 1985 Jun 1;161(6):1326–1343. doi: 10.1084/jem.161.6.1326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Augustin A. A., Sim G. K. T-cell receptors generated via mutations are specific for various major histocompatibility antigens. Cell. 1984 Nov;39(1):5–12. doi: 10.1016/0092-8674(84)90186-7. [DOI] [PubMed] [Google Scholar]
- Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
- Behlke M. A., Spinella D. G., Chou H. S., Sha W., Hartl D. L., Loh D. Y. T-cell receptor beta-chain expression: dependence on relatively few variable region genes. Science. 1985 Aug 9;229(4713):566–570. doi: 10.1126/science.3875151. [DOI] [PubMed] [Google Scholar]
- Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caccia N., Kronenberg M., Saxe D., Haars R., Bruns G. A., Goverman J., Malissen M., Willard H., Yoshikai Y., Simon M. The T cell receptor beta chain genes are located on chromosome 6 in mice and chromosome 7 in humans. Cell. 1984 Jul;37(3):1091–1099. doi: 10.1016/0092-8674(84)90443-4. [DOI] [PubMed] [Google Scholar]
- Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Davis M. M. Molecular genetics of the T cell-receptor beta chain. Annu Rev Immunol. 1985;3:537–560. doi: 10.1146/annurev.iy.03.040185.002541. [DOI] [PubMed] [Google Scholar]
- Epplen J. T., Ali S., Rinaldy A., Simon M. M. The change of specificity, karyotype, and antigen-receptor gene expression is correlated in cytotoxic T-cell lines. Curr Top Microbiol Immunol. 1986;126:69–74. doi: 10.1007/978-3-642-71152-7_9. [DOI] [PubMed] [Google Scholar]
- Gascoigne N. R., Chien Y., Becker D. M., Kavaler J., Davis M. M. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes. Nature. 1984 Aug 2;310(5976):387–391. doi: 10.1038/310387a0. [DOI] [PubMed] [Google Scholar]
- Goverman J., Minard K., Shastri N., Hunkapiller T., Hansburg D., Sercarz E., Hood L. Rearranged beta T cell receptor genes in a helper T cell clone specific for lysozyme: no correlation between V beta and MHC restriction. Cell. 1985 Apr;40(4):859–867. doi: 10.1016/0092-8674(85)90345-9. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Germain R. N., Bevan M. J., Dorf M., Engel I., Fink P., Gascoigne N., Heber-Katz E., Kapp J., Kaufmann Y. Rearrangement and transcription of a T-cell receptor beta-chain gene in different T-cell subsets. Proc Natl Acad Sci U S A. 1985 Jan;82(2):531–535. doi: 10.1073/pnas.82.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hood L., Kronenberg M., Hunkapiller T. T cell antigen receptors and the immunoglobulin supergene family. Cell. 1985 Feb;40(2):225–229. doi: 10.1016/0092-8674(85)90133-3. [DOI] [PubMed] [Google Scholar]
- Kappler J., Kubo R., Haskins K., Hannum C., Marrack P., Pigeon M., McIntyre B., Allison J., Trowbridge I. The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: identification of constant and variable peptides. Cell. 1983 Nov;35(1):295–302. doi: 10.1016/0092-8674(83)90232-5. [DOI] [PubMed] [Google Scholar]
- Lee N. E., D'Eustachio P., Pravtcheva D., Ruddle F. H., Hedrick S. M., Davis M. M. Murine T cell receptor beta chain is encoded on chromosome 6. J Exp Med. 1984 Sep 1;160(3):905–913. doi: 10.1084/jem.160.3.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malissen M., Minard K., Mjolsness S., Kronenberg M., Goverman J., Hunkapiller T., Prystowsky M. B., Yoshikai Y., Fitch F., Mak T. W. Mouse T cell antigen receptor: structure and organization of constant and joining gene segments encoding the beta polypeptide. Cell. 1984 Jul;37(3):1101–1110. doi: 10.1016/0092-8674(84)90444-6. [DOI] [PubMed] [Google Scholar]
- McIntyre B. W., Allison J. P. The mouse T cell receptor: structural heterogeneity of molecules of normal T cells defined by xenoantiserum. Cell. 1983 Oct;34(3):739–746. doi: 10.1016/0092-8674(83)90530-5. [DOI] [PubMed] [Google Scholar]
- Miyada C. G., Klofelt C., Reyes A. A., McLaughlin-Taylor E., Wallace R. B. Evidence that polymorphism in the murine major histocompatibility complex may be generated by the assortment of subgene sequences. Proc Natl Acad Sci U S A. 1985 May;82(9):2890–2894. doi: 10.1073/pnas.82.9.2890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patten P., Yokota T., Rothbard J., Chien Y., Arai K., Davis M. M. Structure, expression and divergence of T-cell receptor beta-chain variable regions. Nature. 1984 Nov 1;312(5989):40–46. doi: 10.1038/312040a0. [DOI] [PubMed] [Google Scholar]
- Rinaldy A., Wallace R. B., Simon M. M., Becker A., Epplen J. T. A highly homologous T-cell receptor beta-chain variable region is expressed in mouse and human T cells. Immunogenetics. 1985;21(4):403–406. doi: 10.1007/BF00430805. [DOI] [PubMed] [Google Scholar]
- Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
- Simon M. M., Weltzien H. U., Bühring H. J., Eichmann K. Aged murine killer T-cell clones acquire specific cytotoxicity for P815 mastocytoma cells. Nature. 1984 Mar 22;308(5957):367–370. doi: 10.1038/308367a0. [DOI] [PubMed] [Google Scholar]
- Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
- Weinstock R., Sweet R., Weiss M., Cedar H., Axel R. Intragenic DNA spacers interrupt the ovalbumin gene. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1299–1303. doi: 10.1073/pnas.75.3.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Doherty P. C. H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;. J Exp Med. 1975 Jun 1;141(6):1427–1436. doi: 10.1084/jem.141.6.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]






