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Gene Review

Cd8a  -  CD8 antigen, alpha chain

Mus musculus

Synonyms: BB154331, Ly-2, Ly-35, Ly-B, Lyt-2, ...
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Disease relevance of Cd8a

  • Studies examining the possible linkage of low lymphoma incidence to a number of loci failed to establish any clear association, but linkage was seen between the Lyt-2 locus and a significant delay in MCA-induced lymphoma development [1].
  • The Thy-1.2, Lyt-2, and T-30 differentiation antigens were not detected on any B lymphoma or plasmacytoma [2].
  • Gene cloning analysis of one mutant demonstrated that the structural rearrangement was due to insertion of an SL3-3 provirus 35 kb 5' to the Lyt-2 gene [3].
  • Mab to LFA-1 and Lyt 2 inhibited LAK activity towards EL-4, YAC-1 and differentiated F-9 teratocarcinoma cells, but did not affect LAK-mediated killing of undifferentiated F-9 cells [4].
  • Using anti-Thy-1,2; Ly-1; Ly-2, antibody and complement, it was suggested that T cells, especially Ly-1,2,3+ T cell populations in the primed nylon-wool adherent cells, play an important role in the induction of systemic amyloidosis [5].

High impact information on Cd8a


Chemical compound and disease context of Cd8a


Biological context of Cd8a

  • The nucleotide sequence of cDNA clones encoding each of these polypeptide chains has been determined and shows the difference between the two Lyt-2 polypeptide chains to be in the lengths of their cytoplasmic tails [8].
  • Comparison of the alpha cDNA with genomic sequence data indicates that there are five exons encoding Lyt-2: a fused leader/immunoglobulin variable region-like exon, a spacer region exon, a transmembrane exon, and two cytoplasmic exons [11].
  • By screening a mouse thymus cDNA library with the Lyt-2 cDNA clone, we isolated two classes of cDNA clones, alpha and alpha', which differ by 31 base pairs [11].
  • These data thus demonstrate that a subpopulation of IL 2-producing cells with a Thy-1+ Lyt-2- surface phenotype can develop in the apparent absence of thymic influence [12].
  • The locus controlling the presence or absence of the determinant mapped 9.8 +/- 2.2 centimorgans from the Igk/Ly-2 locus on chromosome 6 in mice, and may be the beta-chain locus [13].

Anatomical context of Cd8a

  • These results indicate that E8(III) is one of the cis-elements that contribute to the activation of the Cd8a and Cd8b gene complex during T cell development [14].
  • In addition, a small subpopulation comprising 2-3% of cells in the thymus and expressing neither Lyt-2 nor L3T4 has recently been described [15].
  • Although lymph node T cells have only the alpha form of Lyt-2 protein, S1 nuclease analysis shows that lymph nodes have about 20% alpha' mRNA relative to alpha [11].
  • In fact, all anti-Lyt-2 mAbs tested were able to inhibit the IL-2 response of the Lyt-2- and L3T4-deficient cell line HT-2 after transfection with a Lyt-2 cDNA clone [16].
  • We have constructed expression vectors with alpha and alpha' cDNAs and have shown that L-cell transfectants of these produce Lyt-2 polypeptides of the predicted sizes and that these associate as homodimers on the cell membranes [11].

Associations of Cd8a with chemical compounds

  • The Lyt-2/3 molecule is a glycoprotein expressed on T lymphocytes and has classically been considered a marker for the cytotoxic/suppressor T cell subset [8].
  • However, Lyt-1, Lyt-2, surface Ig, IE, MAC-1, and Fc and C3 receptor markers were not detected [17].
  • The previously reported close association of K with Lyt-1 and of D with Lyt-2 were demonstrable equally with unfixed and paraformaldehyde-fixed thymocytes [18].
  • We previously reported that CD25 (IL-2R p55)-positive CD3-CD4-CD8- murine thymocytes can be induced to express CD8 alpha (Lyt-2) by transforming growth factor-beta plus TNF-alpha in the presence of IL-7 (which is necessary to maintain the viability and differentiation capacity of CD25+CD3-CD4-CD8- thymocytes in vitro) [19].
  • The population obtained was shown to be more than 95% positive for the cell marker asialo-GM1, and negative for both Lyt-1 (CD5) and Lyt-2 (CD8) [20].

Physical interactions of Cd8a

  • The expression of L3T4/Lyt-2 on murine T cells has led to the association of these surface markers with recognition of either class II or class I major histo-compatibility complex (MHC) antigens [21].
  • This factor is composed of at least two subunits which come from cells expressing different Ly phenotypes; an antigen-specific antigen-binding "subfactor" is made by an Ly-1 cell and a non-antigen-binding one is made by an Ly-2 cell [22].

Regulatory relationships of Cd8a

  • By using negative selection with monoclonal antibodies plus complement, IL 2 production in aged nude mice was shown to depend upon a subpopulation of cells that expressed Thy-1 but not Lyt-2 [12].
  • Of 15 cytokines tested, only transforming growth factor (TGF-beta) and TNF-alpha induced CD8 (Lyt-2), while no cytokine was able to induce CD4 on CD25+CD3-CD4-CD8- thymocytes [23].
  • Thus the Lyt-3 gene is not subject to the same negative regulatory influences as the Lyt-2 gene [24].
  • Monoclonal antibody to Lyt 2 antigen blocks H-2I- and H-2K- specific mouse cytotoxic T cells [25].
  • Almost all of these Lyt-1 dull T cells expressed magnitudes of L3T4 or Lyt-2 Ag comparable to those detected on Lyt-1 bright T cells [26].

Other interactions of Cd8a


Analytical, diagnostic and therapeutic context of Cd8a

  • All the proliferating cells are Thy1+, some of them express Lyt2 but none has detectable L3T4 T cell differentiation antigens nor T cell antigen receptor (F23.1) on the cell membrane as assessed by immunofluorescence staining and flow fluorocytometry analysis [32].
  • 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 [33].
  • However, phenotypic analysis by using flow microfluorometry and monoclonal antibodies to Lyt-2 and L3T4 showed little differentiation among proliferating 2-4-fetal thymocytes [34].
  • Southern blotting analysis indicated that both mutants had structural rearrangements within or immediately 3' of the Lyt-3 gene, accompanied by demethylation of at least one Hpa II site within the Lyt-2 gene [3].
  • Under these conditions induction of Ly 2 surface antigen was not detected and prothymocytes at the end of the coculture did not manifest IL-1 or mitogen responsiveness [35].


  1. Genetic control of resistance to 3-methylcholanthrene-induced T-cell lymphoma in mice. Ishizaka, S.T., Lilly, F. Cancer Res. (1989) [Pubmed]
  2. Quantitative immunofluorescent analysis of surface phenotypes of murine B cell lymphomas and plasmacytomas with monoclonal antibodies. Lanier, L.L., Warner, N.L., Ledbetter, J.A., Herzenberg, L.A. J. Immunol. (1981) [Pubmed]
  3. Activation of Lyt-2 associated with distant upstream insertion of an SL3-3 provirus. Anson, D.S., Clarkin, K., Hyman, R. Immunogenetics (1992) [Pubmed]
  4. Functionally involved cell surface antigens on murine lymphokine activated killer cells. Belfrage, H., Bhiladvala, P., Kalland, T. Immunol. Lett. (1987) [Pubmed]
  5. Experimental systemic amyloidosis induced by immunization with syngeneic organ extracts in mice. Mori, Y., Akikusa, B., Mori, T., Ueda, S., Iesato, K., Yoshida, H., Ogawa, M., Kato, I., Wakashin, Y., Wakashin, M. J. Exp. Med. (1986) [Pubmed]
  6. CD8 is needed for development of cytotoxic T cells but not helper T cells. Fung-Leung, W.P., Schilham, M.W., Rahemtulla, A., Kündig, T.M., Vollenweider, M., Potter, J., van Ewijk, W., Mak, T.W. Cell (1991) [Pubmed]
  7. Reconstitution of MHC class I specificity by transfer of the T cell receptor and Lyt-2 genes. Gabert, J., Langlet, C., Zamoyska, R., Parnes, J.R., Schmitt-Verhulst, A.M., Malissen, B. Cell (1987) [Pubmed]
  8. Two Lyt-2 polypeptides arise from a single gene by alternative splicing patterns of mRNA. Zamoyska, R., Vollmer, A.C., Sizer, K.C., Liaw, C.W., Parnes, J.R. Cell (1985) [Pubmed]
  9. Regulatory effect of lymphokine-activated killer cells on epidermal proliferation induced by cholera toxin in mice. Okamoto, Y., Tanaka, N., Orita, K. Acta Med. Okayama (1994) [Pubmed]
  10. Induction of tumor suppression and delayed-type footpad reaction by transfer of lymphocytes sensitized to a xenogenized tumor variant. Bianchi, R., Romani, L., Puccetti, P., Fioretti, M.C. Int. J. Cancer (1988) [Pubmed]
  11. Formal proof that different-size Lyt-2 polypeptides arise from differential splicing and post-transcriptional regulation. Tagawa, M., Nakauchi, H., Herzenberg, L.A., Nolan, G.P. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  12. Interleukin 2 production by lymphoid cells from congenitally athymic (nu/nu) mice. MacDonald, H.R., Lees, R.K., Glasebrook, A.L., Sordat, B. J. Immunol. (1982) [Pubmed]
  13. The major histocompatibility complex-restricted antigen receptor on T cells: the genetics of expression of an allotype. Roehm, N.W., Carbone, A., Kushnir, E., Taylor, B.A., Riblet, R.J., Marrack, P., Kappler, J.W. J. Immunol. (1985) [Pubmed]
  14. Functional and molecular analysis of the double-positive stage-specific CD8 enhancer E8III during thymocyte development. Feik, N., Bilic, I., Tinhofer, J., Unger, B., Littman, D.R., Ellmeier, W. J. Immunol. (2005) [Pubmed]
  15. Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. Ceredig, R., Lowenthal, J.W., Nabholz, M., MacDonald, H.R. Nature (1985) [Pubmed]
  16. CD4 and CD8 regulate interleukin 2 responses of T cells. Takahashi, K., Nakata, M., Tanaka, T., Adachi, H., Nakauchi, H., Yagita, H., Okumura, K. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  17. Cloned natural suppressor cell lines derived from the spleens of neonatal mice. Schwadron, R.B., Gandour, D.M., Strober, S. J. Exp. Med. (1985) [Pubmed]
  18. Surface mapping of mouse thymocytes. Flaherty, L., Zimmerman, D. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  19. In vitro induction of CD8 expression on thymic pre-T cells. II. Characterization of CD3-CD4-CD8 alpha + cells generated in vitro by culturing CD25+CD3-CD4-CD8- thymocytes with T cell growth factor-beta and tumor necrosis factor-alpha. Suda, T., Zlotnik, A. J. Immunol. (1992) [Pubmed]
  20. Cytotoxic mechanisms of murine lymphokine-activated killer cells: functional and biochemical characterization of homogeneous populations of spleen LAK cells. Zychlinsky, A., Joag, S., Liu, C.C., Young, J.D. Cell. Immunol. (1990) [Pubmed]
  21. Role of L3T4 in antigen-driven activation of a class I-specific T cell hybridoma. Greenstein, J.L., Malissen, B., Burakoff, S.J. J. Exp. Med. (1985) [Pubmed]
  22. Interactions between molecules (subfactors) released by different T cell sets that yield a complete factor with biological (suppressive) activity. Ptak, W., Rosenstein, R.W., Gershon, R.K. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  23. In vitro induction of CD8 expression on thymic pre-T cells. I. Transforming growth factor-beta and tumor necrosis factor-alpha induce CD8 expression on CD8- thymic subsets including the CD25+CD3-CD4-CD8- pre-T cell subset. Suda, T., Zlotnik, A. J. Immunol. (1992) [Pubmed]
  24. Differential susceptibility of mouse Lyt-2 and Lyt-3 genes to negative regulation. Hwang, I., Gu, J.J., Gottlieb, P.D. Immunogenetics (1993) [Pubmed]
  25. Monoclonal antibody to Lyt 2 antigen blocks H-2I- and H-2K- specific mouse cytotoxic T cells. Miller, R.A., Stutman, O. Nature (1982) [Pubmed]
  26. Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. I. Requirement of Lyt-1 dull L3T4 bright normal T cells for the induction of thyroiditis. Sugihara, S., Izumi, Y., Yoshioka, T., Yagi, H., Tsujimura, T., Tarutani, O., Kohno, Y., Murakami, S., Hamaoka, T., Fujiwara, H. J. Immunol. (1988) [Pubmed]
  27. Molecular linkage of the Ly-3 and Ly-2 genes. Requirement of Ly-2 for Ly-3 surface expression. Gorman, S.D., Sun, Y.H., Zamoyska, R., Parnes, J.R. J. Immunol. (1988) [Pubmed]
  28. Genetic control of the humoral response to an H-2 public specificity. Hansen, T.H., Cullen, S.E., Shinohara, N., Schurko, E., Sachs, D.H. J. Immunol. (1977) [Pubmed]
  29. gamma-Glutamyl cyclotransferase: a new genetic polymorphism in the mouse (Mus musculus) linked to Lyt-2. Tulchin, N., Taylor, B.A. Genetics (1981) [Pubmed]
  30. Linkage of the murine transforming growth factor alpha gene with Igk, Ly-2, and Fabp1 on chromosome 6. Fowler, K.J., Mann, G.B., Dunn, A.R. Genomics (1993) [Pubmed]
  31. Mapping of Igk-V genes using backcrossed laboratory and wild mice. Rueff-Juy, D., Drapier, A.M., Cazenave, P.A. Immunogenetics (1988) [Pubmed]
  32. Recombinant interleukin 4/BSF-1 promotes growth and differentiation of intrathymic T cell precursors from fetal mice in vitro. Palacios, R., Sideras, P., von Boehmer, H. EMBO J. (1987) [Pubmed]
  33. 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. Nakauchi, H., Nolan, G.P., Hsu, C., Huang, H.S., Kavathas, P., Herzenberg, L.A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  34. Proliferation in vitro and interleukin production by 14 day fetal and adult Lyt-2-/L3T4- mouse thymocytes. Ceredig, R. J. Immunol. (1986) [Pubmed]
  35. Interleukin-2 and coculture with thymic epithelial cells synergistically induce prothymocyte differentiation and proliferation. Wiranowska, M., Kaido, T., Caspritz, G., Cook, J., Hadden, J. Thymus (1987) [Pubmed]
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