Abstract
Lyt-3 is a membrane glycoprotein expressed on thymocytes and class I major histocompatibility complex-restricted cytotoxic T cells. Lyt-3 is expressed as a heterodimer with Lyt-2, and this complex is considered to be a homologue of the human Leu-2/T8 (CD8) that has been postulated to be a receptor for the class I major histocompatibility complex. We have determined the complete primary structure of Lyt-3 from the nucleotide sequence of its cDNA clones. Analysis of the predicted amino acid sequence indicates that the Lyt-3 polypeptide has a 21-amino acid leader peptide, and the mature protein consists of an NH2-terminal region of 146 amino acids, a transmembrane region of 27 residues, and a C-terminal region of 19 amino acids. The NH2-terminal 110 residues show clear homology to the T-cell receptor and immunoglobulin variable region sequences. In addition, Lyt-3 has 11 residues that have strong homology to the joining region sequences of the T-cell receptor and the immunoglobulin heavy and light chains. The presence of immunoglobulin variable- as well as joining-region-related sequences in Lyt-3 further supports the idea that these molecules may be recognition molecules belonging to the immunoglobulin super gene family.
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- Arden B., Klotz J. L., Siu G., Hood L. E. Diversity and structure of genes of the alpha family of mouse T-cell antigen receptor. 1985 Aug 29-Sep 4Nature. 316(6031):783–787. doi: 10.1038/316783a0. [DOI] [PubMed] [Google Scholar]
- Boyse E. A., Miyazawa M., Aoki T., Old L. J. Ly-A and Ly-B: two systems of lymphocyte isoantigens in the mouse. Proc R Soc Lond B Biol Sci. 1968 Jun 11;170(1019):175–193. doi: 10.1098/rspb.1968.0032. [DOI] [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Lymphocytes as models for the study of mammalian cellular differentiation. Immunol Rev. 1977 Jan;33:105–124. doi: 10.1111/j.1600-065x.1977.tb00364.x. [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]
- Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [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]
- Gottlieb P. D. Genetic correlation of a mouse light chain variable region marker with a thymocyte surface antigen. J Exp Med. 1974 Nov 1;140(5):1432–1437. doi: 10.1084/jem.140.5.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Habu S., Okumura K. Cell surface antigen marking the stages of murine T cell ontogeny and its functional subsets. Immunol Rev. 1984 Dec;82:117–139. doi: 10.1111/j.1600-065x.1984.tb01120.x. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
- Jay G., Palladino M. A., Khoury G., Old L. J. Mouse Lyt-2 antigen: evidence for two heterodimers with a common subunit. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2654–2657. doi: 10.1073/pnas.79.8.2654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson P., Gagnon J., Barclay A. N., Williams A. F. Purification, chain separation and sequence of the MRC OX-8 antigen, a marker of rat cytotoxic T lymphocytes. EMBO J. 1985 Oct;4(10):2539–2545. doi: 10.1002/j.1460-2075.1985.tb03968.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson P., Williams A. F. Striking similarities between antigen receptor J pieces and sequence in the second chain of the murine CD8 antigen. Nature. 1986 Sep 4;323(6083):74–76. doi: 10.1038/323074a0. [DOI] [PubMed] [Google Scholar]
- Kwan S. P., Max E. E., Seidman J. G., Leder P., Scharff M. D. Two kappa immunoglobulin genes are expressed in the myeloma S107. Cell. 1981 Oct;26(1 Pt 1):57–66. doi: 10.1016/0092-8674(81)90033-7. [DOI] [PubMed] [Google Scholar]
- Ledbetter J. A., Seaman W. E., Tsu T. T., Herzenberg L. A. Lyt-2 and lyt-3 antigens are on two different polypeptide subunits linked by disulfide bonds. Relationship of subunits to T cell cytolytic activity. J Exp Med. 1981 Jun 1;153(6):1503–1516. doi: 10.1084/jem.153.6.1503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lüscher B., Rousseaux-Schmid M., Naim H. Y., MacDonald H. R., Bron C. Biosynthesis and maturation of the Lyt-2/3 molecular complex in mouse thymocytes. J Immunol. 1985 Sep;135(3):1937–1944. [PubMed] [Google Scholar]
- Nakauchi H., Nolan G. P., Hsu C., Huang H. S., Kavathas P., Herzenberg L. A. Molecular cloning of Lyt-2, a membrane glycoprotein marking a subset of mouse T lymphocytes: molecular homology to its human counterpart, Leu-2/T8, and to immunoglobulin variable regions. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5126–5130. doi: 10.1073/pnas.82.15.5126. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakayama E., Shiku H., Stockert E., Oettgen H. F., Old L. J. Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1977–1981. doi: 10.1073/pnas.76.4.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
- Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
- Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shinohara N., Sachs D. H. Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus. J Exp Med. 1979 Sep 19;150(3):432–444. doi: 10.1084/jem.150.3.432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siekevitz M., Gefter M. L., Brodeur P., Riblet R., Marshak-Rothstein A. The genetic basis of antibody production: the dominant anti-arsonate idiotype response of the strain A mouse. Eur J Immunol. 1982 Dec;12(12):1023–1032. doi: 10.1002/eji.1830121208. [DOI] [PubMed] [Google Scholar]
- Snow P. M., Terhorst C. The T8 antigen is a multimeric complex of two distinct subunits on human thymocytes but consists of homomultimeric forms on peripheral blood T lymphocytes. J Biol Chem. 1983 Dec 10;258(23):14675–14681. [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]
- Swain S. L. Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize class 1 major histocompatibility complex antigens regardless of their function. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7101–7105. doi: 10.1073/pnas.78.11.7101. [DOI] [PMC free article] [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]
- 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]
- Tourvieille B., Gorman S. D., Field E. H., Hunkapiller T., Parnes J. R. Isolation and sequence of L3T4 complementary DNA clones: expression in T cells and brain. Science. 1986 Oct 31;234(4776):610–614. doi: 10.1126/science.3094146. [DOI] [PubMed] [Google Scholar]
- Walker I. D., Murray B. J., Kirszbaum L., Chambers G. W., Deacon N. J., McKenzie I. F. The amino-terminal sequences of Ly-2 and Ly-3. Immunogenetics. 1986;23(1):60–63. doi: 10.1007/BF00376523. [DOI] [PubMed] [Google Scholar]
- Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [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]