Abstract
The murine CD8 T cell differentiation antigen is a glycoprotein expressed on the cell surface as a heterodimer comprising the products of two closely linked genes, Ly-2 and Ly-3. The Ly-2 gene encodes, through a mechanism of alternate splicing, two polypeptide chains, alpha and alpha', that differ from one another in the lengths of their cytoplasmic tails. All T cells transcribe and translate both the alpha and alpha' polypeptides of Ly-2 and form heterodimers of each of these polypeptides disulphide-bonded with the Ly-3 polypeptide. However, there is very specific, developmentally controlled regulation of the expression of these heterodimers on the cell surface. Namely, immature T cells show no discrimination of CD8 molecules and express on their cell surface heterodimers containing the Ly-3 polypeptide linked to either the alpha or alpha' chain of Ly-2. In contrast, mature T cells express on their cell surface predominantly the heterodimer containing the Ly-2 alpha chain, the species which has a cytoplasmic tail. Moreover, in mature T cells the complexes which contain the alpha' chain are retained within the cell late in processing. These data emphasize the importance of the CD8 accessory molecule in the development of the functional T cell repertoire and uncover a novel protein sorting mechanism in mature T cells.
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- Acres R. B., Conlon P. J., Mochizuki D. Y., Gallis B. Phosphorylation of the CD8 antigen on cytotoxic human T cells in response to phorbol myristate acetate or antigen-presenting B cells. J Immunol. 1987 Oct 1;139(7):2268–2274. [PubMed] [Google Scholar]
- Blobel G. Intracellular protein topogenesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496–1500. doi: 10.1073/pnas.77.3.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bruce J., Symington F. W., McKearn T. J., Sprent J. A monoclonal antibody discriminating between subsets of T and B cells. J Immunol. 1981 Dec;127(6):2496–2501. [PubMed] [Google Scholar]
- Ceredig R., Glasebrook A. L., MacDonald H. R. Phenotypic and functional properties of murine thymocytes. I. Precursors of cytolytic T lymphocytes and interleukin 2-producing cells are all contained within a subpopulation of "mature" thymocytes as analyzed by monoclonal antibodies and flow microfluorometry. J Exp Med. 1982 Feb 1;155(2):358–379. doi: 10.1084/jem.155.2.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ceredig R., Lowenthal J. W., Nabholz M., MacDonald H. R. Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. Nature. 1985 Mar 7;314(6006):98–100. doi: 10.1038/314098a0. [DOI] [PubMed] [Google Scholar]
- Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. doi: 10.1038/312548a0. [DOI] [PubMed] [Google Scholar]
- Crispe I. N., Bevan M. J. Expression and functional significance of the J11d marker on mouse thymocytes. J Immunol. 1987 Apr 1;138(7):2013–2018. [PubMed] [Google Scholar]
- Dembić Z., Haas W., Zamoyska R., Parnes J., Steinmetz M., von Boehmer H. Transfection of the CD8 gene enhances T-cell recognition. Nature. 1987 Apr 2;326(6112):510–511. doi: 10.1038/326510a0. [DOI] [PubMed] [Google Scholar]
- Doyle C., Roth M. G., Sambrook J., Gething M. J. Mutations in the cytoplasmic domain of the influenza virus hemagglutinin affect different stages of intracellular transport. J Cell Biol. 1985 Mar;100(3):704–714. doi: 10.1083/jcb.100.3.704. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elder J. H., Alexander S. endo-beta-N-acetylglucosaminidase F: endoglycosidase from Flavobacterium meningosepticum that cleaves both high-mannose and complex glycoproteins. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4540–4544. doi: 10.1073/pnas.79.15.4540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emmrich F., Strittmatter U., Eichmann K. Synergism in the activation of human CD8 T cells by cross-linking the T-cell receptor complex with the CD8 differentiation antigen. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8298–8302. doi: 10.1073/pnas.83.21.8298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fan J., Ahmed A., Bonavida B. Studies on the induction and expression of T cell-mediated immunity. X. Inhibition by Lyt 2,3 antisera of cytotoxic T lymphocyte-mediated antigen-specific and -nonspecific cytotoxicity: evidence for the blocking of the binding between T lymphocytes and target cells and not the post-binding cytolytic steps. J Immunol. 1980 Dec;125(6):2444–2453. [PubMed] [Google Scholar]
- Fowlkes B. J., Edison L., Mathieson B. J., Chused T. M. Early T lymphocytes. Differentiation in vivo of adult intrathymic precursor cells. J Exp Med. 1985 Sep 1;162(3):802–822. doi: 10.1084/jem.162.3.802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gabert J., Langlet C., Zamoyska R., Parnes J. R., Schmitt-Verhulst A. M., Malissen B. Reconstitution of MHC class I specificity by transfer of the T cell receptor and Lyt-2 genes. Cell. 1987 Aug 14;50(4):545–554. doi: 10.1016/0092-8674(87)90027-4. [DOI] [PubMed] [Google Scholar]
- Gallagher P. F., Fazekas de St Groth B., Miller J. F. Stable expression of Lyt-2 homodimers on L3T4+ T cell clones. Eur J Immunol. 1986 Nov;16(11):1413–1417. doi: 10.1002/eji.1830161116. [DOI] [PubMed] [Google Scholar]
- Garoff H., Kondor-Koch C., Pettersson R., Burke B. Expression of Semliki Forest virus proteins from cloned complementary DNA. II. The membrane-spanning glycoprotein E2 is transported to the cell surface without its normal cytoplasmic domain. J Cell Biol. 1983 Sep;97(3):652–658. doi: 10.1083/jcb.97.3.652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garoff H. Using recombinant DNA techniques to study protein targeting in the eucaryotic cell. Annu Rev Cell Biol. 1985;1:403–445. doi: 10.1146/annurev.cb.01.110185.002155. [DOI] [PubMed] [Google Scholar]
- Golstein P., Goridis C., Schmitt-Verhulst A. M., Hayot B., Pierres A., van Agthoven A., Kaufmann Y., Eshhar Z., Pierres M. Lymphoid cell surface interaction structures detected using cytolysis-inhibiting monoclonal antibodies. Immunol Rev. 1982;68:5–42. doi: 10.1111/j.1600-065x.1982.tb01058.x. [DOI] [PubMed] [Google Scholar]
- Hollander N. Effects of anti-Lyt antibodies on T-cell functions. Immunol Rev. 1982;68:43–66. doi: 10.1111/j.1600-065x.1982.tb01059.x. [DOI] [PubMed] [Google Scholar]
- Keski-Oja J., Mosher D. F., Vaheri A. Dimeric character of fibronectin, a major cell surface-associated glycoprotein. Biochem Biophys Res Commun. 1977 Jan 24;74(2):699–706. doi: 10.1016/0006-291x(77)90359-x. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Ledbetter J. A., Seaman W. E. The Lyt-2, Lyt-3 macromolecules: structural and functional studies. Immunol Rev. 1982;68:197–218. doi: 10.1111/j.1600-065x.1982.tb01065.x. [DOI] [PubMed] [Google Scholar]
- Liaw C. W., Zamoyska R., Parnes J. R. Structure, sequence, and polymorphism of the Lyt-2 T cell differentiation antigen gene. J Immunol. 1986 Aug 1;137(3):1037–1043. [PubMed] [Google Scholar]
- MacDonald H. R., Budd R. C., Howe R. C. A CD3- subset of CD4-8+ thymocytes: a rapidly cycling intermediate in the generation of CD4+8+ cells. Eur J Immunol. 1988 Apr;18(4):519–523. doi: 10.1002/eji.1830180405. [DOI] [PubMed] [Google Scholar]
- MacDonald H. R., Glasebrook A. L., Bron C., Kelso A., Cerottini J. C. Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on cytolytic T lymphocytes (CTL): possible implications for the affinity of CTL antigen receptors. Immunol Rev. 1982;68:89–115. doi: 10.1111/j.1600-065x.1982.tb01061.x. [DOI] [PubMed] [Google Scholar]
- Marrack P., Endres R., Shimonkevitz R., Zlotnik A., Dialynas D., Fitch F., Kappler J. The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product. J Exp Med. 1983 Oct 1;158(4):1077–1091. doi: 10.1084/jem.158.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McPhee D., Pye J., Shortman K. The differentiation of T lymphocytes. V. Evidence for intrathymic death of most thymocytes. Thymus. 1979 Nov;1(3):151–162. [PubMed] [Google Scholar]
- Murre C., Reiss C. S., Bernabeu C., Chen L. B., Burakoff S. J., Seidman J. G. Construction, expression and recognition of an H-2 molecule lacking its carboxyl terminus. Nature. 1984 Feb 2;307(5950):432–436. doi: 10.1038/307432a0. [DOI] [PubMed] [Google Scholar]
- Nakauchi H., Shinkai Y., Okumura K. Molecular cloning of Lyt-3, a membrane glycoprotein marking a subset of mouse T lymphocytes: molecular homology to immunoglobulin and T-cell receptor variable and joining regions. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4210–4214. doi: 10.1073/pnas.84.12.4210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
- Panaccio M., Gillespie M. T., Walker I. D., Kirszbaum L., Sharpe J. A., Tobias G. H., McKenzie I. F., Deacon N. J. Molecular characterization of the murine cytotoxic T-cell membrane glycoprotein Ly-3 (CD8). Proc Natl Acad Sci U S A. 1987 Oct;84(19):6874–6878. doi: 10.1073/pnas.84.19.6874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pettey C. L., Alarcon B., Malin R., Weinberg K., Terhorst C. T3-p28 is a protein associated with the delta and epsilon chains of the T cell receptor-T3 antigen complex during biosynthesis. J Biol Chem. 1987 Apr 5;262(10):4854–4859. [PubMed] [Google Scholar]
- Reilly E. B., Auditore-Hargreaves K., Hämmerling U., Gottlieb P. D. Lyt-2 and Lyt-3 alloantigens: precipitation with monoclonal and conventional antibodies and analysis on one- and two-dimensional polyacrylamide gels. J Immunol. 1980 Nov;125(5):2245–2251. [PubMed] [Google Scholar]
- Rose J. K., Bergmann J. E. Altered cytoplasmic domains affect intracellular transport of the vesicular stomatitis virus glycoprotein. Cell. 1983 Sep;34(2):513–524. doi: 10.1016/0092-8674(83)90384-7. [DOI] [PubMed] [Google Scholar]
- Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
- Scollay R., Bartlett P., Shortman K. T cell development in the adult murine thymus: changes in the expression of the surface antigens Ly2, L3T4 and B2A2 during development from early precursor cells to emigrants. Immunol Rev. 1984 Dec;82:79–103. doi: 10.1111/j.1600-065x.1984.tb01118.x. [DOI] [PubMed] [Google Scholar]
- Smith L. CD4+ murine T cells develop from CD8+ precursors in vivo. Nature. 1987 Apr 23;326(6115):798–800. doi: 10.1038/326798a0. [DOI] [PubMed] [Google Scholar]
- Swain S. L. T cell subsets and the recognition of MHC class. Immunol Rev. 1983;74:129–142. doi: 10.1111/j.1600-065x.1983.tb01087.x. [DOI] [PubMed] [Google Scholar]
- Tagawa M., Nakauchi H., Herzenberg L. A., Nolan G. P. Formal proof that different-size Lyt-2 polypeptides arise from differential splicing and post-transcriptional regulation. Proc Natl Acad Sci U S A. 1986 May;83(10):3422–3426. doi: 10.1073/pnas.83.10.3422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker I. D., Hogarth P. M., Murray B. J., Lovering K. E., Classon B. J., Chambers G. W., McKenzie I. F. Ly antigens associated with T cell recognition and effector function. Immunol Rev. 1984 Dec;82:47–77. doi: 10.1111/j.1600-065x.1984.tb01117.x. [DOI] [PubMed] [Google Scholar]
- Walker I. D., Murray B. J., Hogarth P. M., Kelso A., McKenzie I. F. Comparison of thymic and peripheral T cell Ly-2/3 antigens. Eur J Immunol. 1984 Oct;14(10):906–910. doi: 10.1002/eji.1830141009. [DOI] [PubMed] [Google Scholar]
- Wills J. W., Srinivas R. V., Hunter E. Mutations of the Rous sarcoma virus env gene that affect the transport and subcellular location of the glycoprotein products. J Cell Biol. 1984 Dec;99(6):2011–2023. doi: 10.1083/jcb.99.6.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zamoyska R., Vollmer A. C., Sizer K. C., Liaw C. W., Parnes J. R. Two Lyt-2 polypeptides arise from a single gene by alternative splicing patterns of mRNA. Cell. 1985 Nov;43(1):153–163. doi: 10.1016/0092-8674(85)90020-0. [DOI] [PubMed] [Google Scholar]
- Zuniga M. C., Hood L. E. Clonal variation in cell surface display of an H-2 protein lacking a cytoplasmic tail. J Cell Biol. 1986 Jan;102(1):1–10. doi: 10.1083/jcb.102.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]