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Gene Review

Cd247  -  CD247 antigen

Mus musculus

Synonyms: 4930549J05Rik, A430104F18Rik, AW552088, CD3 zeta, CD3-eta, ...
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Disease relevance of Cd247


High impact information on Cd247

  • Recent studies have demonstrated that the CD3-zeta subunit of the T cell antigen receptor (TCR) complex is involved in signal transduction [6].
  • One variant produced all CD3/Ti components except CD3-zeta and was able to express small amounts of surface CD3/Ti [7].
  • Surprisingly, in the absence of CD3-zeta, direct cross-linking of the partial receptor induced both phosphatidylinositol hydrolysis and interleukin 2 production [7].
  • These data indicate that CD3-zeta determines the normal intracellular fate of the T cell antigen receptor and is likely to play an important role in physiologically relevant transmembrane signaling [7].
  • Our data indicate that the blockade of positive selection of CD3delta-/- thymocytes may derive from defective tyrosine phosphorylation of CD3zeta in lipid rafts, resulting in impaired activation of the LAT/Ras/ERK pathway [8].

Biological context of Cd247


Anatomical context of Cd247

  • Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-alpha/beta+ T cells and expansion of NK1.1+ TCR-gamma/delta+ T cell development in CD3 zeta-deficient mice [10].
  • Here we identify a new TCR isoform expressed on splenic CD2+, CD3/Ti alpha-beta+, CD4-, CD8-, CD16+, NK1.1+ mouse large granular lymphocytes (LGL), which are devoid of CD3 zeta and CD3 eta proteins [13].
  • However, the development of NK1.1+ TCR-alpha/beta+ T cells was almost completely disrupted in thymus and spleen in CD3 zeta-deficient mice, whereas no alteration was observed in FcR gamma-deficient mice [10].
  • Spleen and lymph nodes of CD3-zeta-/- mutant mice contained a normal number and ratio of CD4+ and CD8+ single positive cells that were TCR/CD3very low [14].
  • Here, we found that the expression of Fc gamma RIII on NK cells from CD3 zeta-deficient mice is unexpectedly up-regulated compared with that on cells from normal mice [15].

Associations of Cd247 with chemical compounds

  • The NH2-terminal sequences of CD3 eta and CD3 zeta are identical through amino acid 122 of each mature protein but then diverge in the remainder of their respective COOH-terminal regions, consistent with alternatively spliced products of a common gene [12].
  • T cell CD3-zeta eta heterodimer expression and coupling to phosphoinositide hydrolysis [16].
  • CD16-II (Fc gamma RIII-2) is expressed on NK cells and macrophages as a transmembrane glycoprotein associated with CD3 zeta or Fc epsilon RI-gamma [17].
  • However, both CD44 mutants with a heterologous transmembrane domain, derived from either the CD3 zeta chain or CD45, were completely soluble in Triton X-100 [18].
  • These results contrast with the classical view that naive T cell survival is associated with CD3zeta phosphorylation and depends mostly on IL-7 and MHC-TCR interactions [19].

Physical interactions of Cd247

  • We show that ZAP-70 fails to bind the signaling-competent CD3zeta tyrosine phosphorylation isoform and to become activated following TCR engagement, suggesting that defective recruitment of ZAP-70 might underlie the TCR signaling dysfunction in these patients [20].
  • We investigated the putative contribution of clonotype-independent CD3 complex signaling to TCRbeta locus allelic exclusion in mice single-deficient or double-deficient for CD3zeta/eta and/or p56(lck) [21].

Regulatory relationships of Cd247

  • These data indicate that signals resulting from exclusive CD3 engagement can influence CD8 molecular associations and activate CD8-bound p56(lck) [22].
  • We conclude that the signal transduction pathways leading to CTL development and cytokine production can be triggered through TCR in the absence of functional CD3zeta, provided the remainder of the TCR-CD3 complex is expressed at high levels on the cell surface [23].
  • Unlike conventional T cells, DNtg TCR alpha beta+NK1.1+ cells from anti-HY/Rag-2(-/-) H-2b mice express Fc(epsilon)RI(gamma) and CD3zeta as DN alpha beta TCR+NK1.1+ cells from normal C57BL/6 mice [24].
  • The high levels of CD3 zeta message expressed in rat NK cells may indicate that other unidentified hetero-subunits are required for assembly of rat CD3 zeta into functional CD16 receptors [25].
  • This feature increases the structural complexity of TCRs by creating "isoforms." Both CD3 zeta and -eta are thought to play an important role in signal transduction triggered by antigen/major histocompatibility complex [26].

Other interactions of Cd247


Analytical, diagnostic and therapeutic context of Cd247


  1. The single positive T cells found in CD3-zeta/eta-/- mice overtly react with self-major histocompatibility complex molecules upon restoration of normal surface density of T cell receptor-CD3 complex. Lin, S.Y., Ardouin, L., Gillet, A., Malissen, M., Malissen, B. J. Exp. Med. (1997) [Pubmed]
  2. T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP-70, and CD3 zeta despite suppressed cytolytic activity. Levey, D.L., Srivastava, P.K. J. Exp. Med. (1995) [Pubmed]
  3. Variable expression of CD3-zeta chain in tumor-infiltrating lymphocytes (TIL) derived from renal-cell carcinoma: relationship with TIL phenotype and function. Tartour, E., Latour, S., Mathiot, C., Thiounn, N., Mosseri, V., Joyeux, I., D'Enghien, C.D., Lee, R., Debre, B., Fridman, W.H. Int. J. Cancer (1995) [Pubmed]
  4. Correlation between disease activity and T-cell CD3 zeta chain expression in a B-cell lymphoma. Massaia, M., Attisano, C., Beggiato, E., Bianchi, A., Pileri, A. Br. J. Haematol. (1994) [Pubmed]
  5. L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. Rodriguez, P.C., Zea, A.H., DeSalvo, J., Culotta, K.S., Zabaleta, J., Quiceno, D.G., Ochoa, J.B., Ochoa, A.C. J. Immunol. (2003) [Pubmed]
  6. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Wegener, A.M., Letourneur, F., Hoeveler, A., Brocker, T., Luton, F., Malissen, B. Cell (1992) [Pubmed]
  7. Failure to synthesize the T cell CD3-zeta chain: structure and function of a partial T cell receptor complex. Sussman, J.J., Bonifacino, J.S., Lippincott-Schwartz, J., Weissman, A.M., Saito, T., Klausner, R.D., Ashwell, J.D. Cell (1988) [Pubmed]
  8. CD3delta couples T-cell receptor signalling to ERK activation and thymocyte positive selection. Delgado, P., Fernández, E., Dave, V., Kappes, D., Alarcón, B. Nature (2000) [Pubmed]
  9. Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Tomasello, E., Desmoulins, P.O., Chemin, K., Guia, S., Cremer, H., Ortaldo, J., Love, P., Kaiserlian, D., Vivier, E. Immunity (2000) [Pubmed]
  10. Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-alpha/beta+ T cells and expansion of NK1.1+ TCR-gamma/delta+ T cell development in CD3 zeta-deficient mice. Arase, H., Ono, S., Arase, N., Park, S.Y., Wakizaka, K., Watanabe, H., Ohno, H., Saito, T. J. Exp. Med. (1995) [Pubmed]
  11. Targeted disruption of the CD3 eta locus causes high lethality in mice: modulation of Oct-1 transcription on the opposite strand. Ohno, H., Goto, S., Taki, S., Shirasawa, T., Nakano, H., Miyatake, S., Aoe, T., Ishida, Y., Maeda, H., Shirai, T. EMBO J. (1994) [Pubmed]
  12. Molecular cloning of the CD3 eta subunit identifies a CD3 zeta-related product in thymus-derived cells. Jin, Y.J., Clayton, L.K., Howard, F.D., Koyasu, S., Sieh, M., Steinbrich, R., Tarr, G.E., Reinherz, E.L. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  13. T cell receptor complexes containing Fc epsilon RI gamma homodimers in lieu of CD3 zeta and CD3 eta components: a novel isoform expressed on large granular lymphocytes. Koyasu, S., D'Adamio, L., Arulanandam, A.R., Abraham, S., Clayton, L.K., Reinherz, E.L. J. Exp. Med. (1992) [Pubmed]
  14. Abnormal T cell development in CD3-zeta-/- mutant mice and identification of a novel T cell population in the intestine. Liu, C.P., Ueda, R., She, J., Sancho, J., Wang, B., Weddell, G., Loring, J., Kurahara, C., Dudley, E.C., Hayday, A. EMBO J. (1993) [Pubmed]
  15. Negative regulation of expression and function of Fc gamma RIII by CD3 zeta in murine NK cells. Arase, H., Suenaga, T., Arase, N., Kimura, Y., Ito, K., Shiina, R., Ohno, H., Saito, T. J. Immunol. (2001) [Pubmed]
  16. T cell CD3-zeta eta heterodimer expression and coupling to phosphoinositide hydrolysis. Merćep, M., Bonifacino, J.S., Garcia-Morales, P., Samelson, L.E., Klausner, R.D., Ashwell, J.D. Science (1988) [Pubmed]
  17. Involvement of a metalloprotease in spontaneous and phorbol ester-induced release of natural killer cell-associated Fc gamma RIII (CD16-II). Harrison, D., Phillips, J.H., Lanier, L.L. J. Immunol. (1991) [Pubmed]
  18. Transmembrane domain of CD44 is required for its detergent insolubility in fibroblasts. Perschl, A., Lesley, J., English, N., Hyman, R., Trowbridge, I.S. J. Cell. Sci. (1995) [Pubmed]
  19. Multiple survival signals are delivered by dendritic cells to naive CD4+ T cells. Feuillet, V., Lucas, B., Di Santo, J.P., Bismuth, G., Trautmann, A. Eur. J. Immunol. (2005) [Pubmed]
  20. Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects. Boncristiano, M., Majolini, M.B., D'Elios, M.M., Pacini, S., Valensin, S., Ulivieri, C., Amedei, A., Falini, B., Del Prete, G., Telford, J.L., Baldari, C.T. Eur. J. Immunol. (2000) [Pubmed]
  21. Regulation of T cell receptor (TCR) beta gene expression by CD3 complex signaling in immature thymocytes: implications for TCRbeta allelic exclusion. Biro, J., Würch, A., Potocnik, A.J., Falk, I., Mossmann, H., Eichmann, K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  22. Influence on CD8 of TCR/CD3-generated signals in CTL clones and CTL precursor cells. Anel, A., Martínez-Lorenzo, M.J., Schmitt-Verhulst, A.M., Boyer, C. J. Immunol. (1997) [Pubmed]
  23. Generation of antigen-specific cytotoxic T lymphocytes and regulation of cytokine production takes place in the absence of CD3zeta. She, J., Ruzek, M.C., Velupillai, P., de Aos, I., Wang, B., Harn, D.A., Sancho, J., Biron, C.A., Terhorst, C. Int. Immunol. (1999) [Pubmed]
  24. Development of CD4-CD8- alpha beta TCR+NK1.1+ T lymphocytes: thymic selection by self antigen. Schulz, R.J., Parkes, A., Mizoguchi, E., Bhan, A.K., Koyasu, S. J. Immunol. (1996) [Pubmed]
  25. Rat class III Fc gamma receptor isoforms differ in IgG subclass-binding specificity and fail to associate productively with rat CD3 zeta. Farber, D.L., Giorda, R., Nettleton, M.Y., Trucco, M., Kochan, J.P., Sears, D.W. J. Immunol. (1993) [Pubmed]
  26. Differential signal transduction via T-cell receptor CD3 zeta 2, CD3 zeta-eta, and CD3 eta 2 isoforms. Bauer, A., McConkey, D.J., Howard, F.D., Clayton, L.K., Novick, D., Koyasu, S., Reinherz, E.L. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  27. Development and function of T cells in T cell antigen receptor/CD3 zeta knockout mice reconstituted with Fc epsilon RI gamma. Liu, C.P., Lin, W.J., Huang, M., Kappler, J.W., Marrack, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  28. Differential Src family kinase activity requirements for CD3 zeta phosphorylation/ZAP70 recruitment and CD3 epsilon phosphorylation. Lysechko, T.L., Ostergaard, H.L. J. Immunol. (2005) [Pubmed]
  29. Expression and selection of productively rearranged TCR beta VDJ genes are sequentially regulated by CD3 signaling in the development of NK1.1(+) alpha beta T cells. Baur, N., Nerz, G., Nil, A., Eichmann, K. Int. Immunol. (2001) [Pubmed]
  30. Increased Zap-70 association with CD3zeta in CD4 T cells from old mice. Garcia, G.G., Miller, R.A. Cell. Immunol. (1998) [Pubmed]
  31. Developmental and functional impairment of T cells in mice lacking CD3 zeta chains. Ohno, H., Aoe, T., Taki, S., Kitamura, D., Ishida, Y., Rajewsky, K., Saito, T. EMBO J. (1993) [Pubmed]
  32. Architectural changes in the TCR:CD3 complex induced by MHC:peptide ligation. La Gruta, N.L., Liu, H., Dilioglou, S., Rhodes, M., Wiest, D.L., Vignali, D.A. J. Immunol. (2004) [Pubmed]
  33. T cell receptor-independent CD2 signal transduction in FcR+ cells. Arulanandam, A.R., Koyasu, S., Reinherz, E.L. J. Exp. Med. (1991) [Pubmed]
  34. Reconstitution of CD3 zeta coupling to calcium mobilization via genetic complementation. Donnadieu, E., Trautmann, A., Malissen, M., Trucy, J., Malissen, B., Vivier, E. J. Biol. Chem. (1994) [Pubmed]
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