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Gene Review

Ly6c1  -  lymphocyte antigen 6 complex, locus C1

Mus musculus

Synonyms: AA682074, AA959465, Ly-6C, Ly-6C1, Ly6c
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High impact information on Ly6c

  • Developmentally, CD4+CD8- thymocytes leave the thymus expressing low levels of Ly6C; 3 days later approximately 50% stably upregulate Ly6C without cell division or TCR engagement in the periphery [1].
  • Our results show that the majority of primed CD8+ T cells generated in this system are not cycling and express increased levels of CD44 and Ly6C [2].
  • Here we show that a significant fraction of these autoreactive cells in the normal adult thymus expresses NK1.1 and high levels of Ly-6C and also exhibits flexibility in MHC restriction [3].
  • The murine alloantigen, Ly-6C, is found on 45% of bone marrow cells, 25% of splenocytes and 15% of lymph node cells in all inbred strains of mice tested, with the exception of NOD, NZB and ST [4].
  • A recombination event in the 5' flanking region of the Ly-6C gene correlates with impaired expression in the NOD, NZB and ST strains of mice [4].

Biological context of Ly6c


Anatomical context of Ly6c

  • In these three strains, Ly-6C expression can be detected on only 5% of bone marrow cells and not at all on cells from spleen or lymph node [4].
  • Ly-6 superfamily members Ly-6A/E, Ly-6C, and Ly-6I recognize two potential ligands expressed by B lymphocytes [7].
  • In the capillary flow-adhesion assay, Ly6C cross-linking significantly augments lymphocyte adhesion to endothelium, and this is inhibited by an Ab that blocks LFA-1 function [6].
  • Primary osteoblasts and MC3T3 cells constitutively expressed both Ly-6A and Ly-6C antigens, although Ly-6C was much less abundant [8].
  • Multiple expression of Ly-6C and accumulation of a Ly-6C pre-mRNA in activated macrophages involved in rejection of an allografted tumor [9].

Associations of Ly6c with chemical compounds

  • Despite results indicating fewer disulfide constraints in the Ly-6C molecule, the predicted sequence contains 10 cysteine residues nearly perfectly matched with those predicted in Ly-6A [10].
  • Moreover, they were not stimulated, in the presence of PMA, by doses of ionomycin that were optimal for normal T cells, but did respond to higher ionomycin concentrations (2 micrograms/ml), and this response was not altered by Ly-6C cross-linking [11].
  • Using subtractive cDNA hybridization we have identified the cell surface protein Ly6C as differentially expressed on B cells stimulated with LPS only [12].

Regulatory relationships of Ly6c

  • In vivo studies demonstrated that proinflammatory (Th1) cytokines transiently upregulate B cell Ly-6C expression [13].
  • The abilities of Ly6C to induce LFA-1 clustering and to be re-expressed after signaling-associated down-regulation may be important in regulating the homing of CD8 T cells into lymph nodes and in subsequent steps of CD8 T cell activation and effector function that again involve LFA-1 [6].
  • However, Ly-6I is also expressed on immature B cell populations that do not express Ly-6C [14].
  • We compared Ly-6C expression on neutrophils and monocytes following short-term cell activation induced by C5a or phorbol esters or treatment with phosphatidylinositol-specific phospholipase-C (PI-PLC) [15].
  • It was found that both Ly-6A/E and T cell-activating protein (TAP) molecules are markedly enhanced while Ly-6C is less affected [16].

Other interactions of Ly6c

  • CH27 cells with low levels of Ly-6A/E ligand activity also lost expression of CD22, and cells transfected with CD22 gained the ability to bind the Ly-6A/E chimera and, to a lesser extent, the Ly-6C and Ly-6I chimeric proteins [7].
  • For T lymphocytes from BALB/c (Ly-6.1) mice, Ly-6A/E, but not Ly-6C, molecules were synergistically induced by IFN-gamma and TNF [17].
  • Although endogenous Ly-6A.2 and Ly-6C genes are IFN responsive, only the latter contains a clearly identifiable IFN responsive element [18].
  • This renal expression and its interferon (IFN)-gamma inducibility in murine strains expressing different Ly-6 haplotypes were studied with monoclonal antibodies and cDNA probes that recognize Ly-6A/E and Ly-6C [19].
  • Polyclonal B cell activators (anti-IgM and recombinant CD40 ligand trimer) showed minimal ability to independently induce Ly-6C expression on B cells but did enhance the ability of IFNs to induce expression [13].

Analytical, diagnostic and therapeutic context of Ly6c


  1. Developmentally distinct Th cells control plasma cell production in vivo. McHeyzer-Williams, L.J., McHeyzer-Williams, M.G. Immunity (2004) [Pubmed]
  2. Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro. Pihlgren, M., Dubois, P.M., Tomkowiak, M., Sjögren, T., Marvel, J. J. Exp. Med. (1996) [Pubmed]
  3. Altered major histocompatibility complex restriction in the NK1.1+Ly-6Chi autoreactive CD4+ T cell subset from class II-deficient mice. Kariv, I., Hardy, R.R., Hayakawa, K. J. Exp. Med. (1994) [Pubmed]
  4. A recombination event in the 5' flanking region of the Ly-6C gene correlates with impaired expression in the NOD, NZB and ST strains of mice. Philbrick, W.M., Maher, S.E., Bridgett, M.M., Bothwell, A.L. EMBO J. (1990) [Pubmed]
  5. Fate and function of anti-CD3/CD28-activated T cells following adoptive transfer: IL-2 promotes development of anti-tumor memory T cells in vivo. Hughes, D.P., Baskar, D., Urban, F.F., Friedman, M.S., Braun, T.M., McDonagh, K.T. Cytotherapy. (2005) [Pubmed]
  6. Ly6C induces clustering of LFA-1 (CD11a/CD18) and is involved in subtype-specific adhesion of CD8 T cells. Jaakkola, I., Merinen, M., Jalkanen, S., Hänninen, A. J. Immunol. (2003) [Pubmed]
  7. Ly-6 superfamily members Ly-6A/E, Ly-6C, and Ly-6I recognize two potential ligands expressed by B lymphocytes. Pflugh, D.L., Maher, S.E., Bothwell, A.L. J. Immunol. (2002) [Pubmed]
  8. Expression and regulation of Ly-6 differentiation antigens by murine osteoblasts. Horowitz, M.C., Fields, A., DeMeo, D., Qian, H.Y., Bothwell, A.L., Trepman, E. Endocrinology (1994) [Pubmed]
  9. Multiple expression of Ly-6C and accumulation of a Ly-6C pre-mRNA in activated macrophages involved in rejection of an allografted tumor. Takikawa, O., Oku, T., Ito, N., Ushio, Y., Yamamoto, N., Yoneda, Y., Tsuji, J., Sanchez-Bueno, A., Verkhusha, V., Yoshida, R. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  10. N-terminal and cDNA characterization of murine lymphocyte antigen Ly-6C.2. Palfree, R.G., Sirlin, S., Dumont, F.J., Hämmerling, U. J. Immunol. (1988) [Pubmed]
  11. Stimulation of murine T cells via the Ly-6C antigen: lack of proliferative response in aberrant T cells from lpr/lpr and gld/gld mice despite high Ly-6C antigen expression. Dumont, F.J. J. Immunol. (1987) [Pubmed]
  12. Ly6C expression differentiates plasma cells from other B cell subsets in mice. Wrammert, J., Källberg, E., Agace, W.W., Leanderson, T. Eur. J. Immunol. (2002) [Pubmed]
  13. B cells express Ly-6C in a Th1 but not Th2 cytokine environment. Schlueter, A.J., Krieg, A.M., De Vries, P., Li, X. J. Interferon Cytokine Res. (2002) [Pubmed]
  14. Ly-6I, a new member of the murine Ly-6 superfamily with a distinct pattern of expression. Pflugh, D.L., Maher, S.E., Bothwell, A.L. J. Immunol. (2000) [Pubmed]
  15. Differences in the expression of Ly-6C on neutrophils and monocytes following PI-PLC hydrolysis and cellular activation. Jutila, D.B., Kurk, S., Jutila, M.A. Immunol. Lett. (1994) [Pubmed]
  16. Selective up-regulation by interferon-gamma of surface molecules of the Ly-6 complex in resting T cells: the Ly-6A/E and TAP antigens are preferentially enhanced. Dumont, F.J., Dijkmans, R., Palfree, R.G., Boltz, R.D., Coker, L. Eur. J. Immunol. (1987) [Pubmed]
  17. Tumor necrosis factor synergistically acts with IFN-gamma to regulate Ly-6A/E expression in T lymphocytes, thymocytes and bone marrow cells. Malek, T.R., Danis, K.M., Codias, E.K. J. Immunol. (1989) [Pubmed]
  18. Isolation, expression, and sequence of the TAP/Ly-6A.2 chromosomal gene. McGrew, J.T., Rock, K.L. J. Immunol. (1991) [Pubmed]
  19. Ly-6 in kidney is widely expressed on tubular epithelium and vascular endothelium and is up-regulated by interferon gamma. Blake, P.G., Madrenas, J., Halloran, P.F. J. Am. Soc. Nephrol. (1993) [Pubmed]
  20. Ly-6C is a marker of memory CD8+ T cells. Walunas, T.L., Bruce, D.S., Dustin, L., Loh, D.Y., Bluestone, J.A. J. Immunol. (1995) [Pubmed]
  21. Functionally anergic lpr and gld B220+ T cell receptor (TCR)-alpha/beta+ double-negative T cells express CD28 and respond to costimulation with phorbol myristate acetate and antibodies to CD28 and the TCR. Giese, T., Allison, J.P., Davidson, W.F. J. Immunol. (1993) [Pubmed]
  22. Ly-6C is expressed in brain vessels endothelial cells but not in microglia of the mouse. Alliot, F., Rutin, J., Pessac, B. Neurosci. Lett. (1998) [Pubmed]
  23. Recombinant human interferon-alpha A/D enhances the expression of Ly-6A/E, Ly-6C, and TAP antigens on murine T lymphocytes. Dumont, F.J. J. Interferon Res. (1988) [Pubmed]
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