التفاصيل البيبلوغرافية
| العنوان: |
An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells |
| المؤلفون: |
Vijayakrishnan, Lalitha1, Slavik, Jacqueline M.1, Illés, Zsolt1, Greenwald, Rebecca J.2, Rainbow, Dan3, Greve, Bernhard1, Peterson, Laurence B.4, Hafler, David A.1, Freeman, Gordon J.5, Sharpe, Arlene H.2, Wicker, Linda S.3 linda.wicker@cimr.cam.ac.uk, Kuchroo, Vijay K.1 vkuchroo@rics.bwh.harvard.edu |
| المصدر: |
Immunity (10747613). May2004, Vol. 20 Issue 5, p563-575. 13p. |
| مصطلحات موضوعية: |
*AUTOIMMUNE diseases, *T cells, *LYMPHOCYTES, *PROTEINS |
| مستخلص: |
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulating T cell responses. A number of autoimmune diseases have shown genetic linkage to the CTLA-4 locus. We have cloned and expressed an alternatively spliced form of CTLA-4 that has genetic linkage with type I diabetes in the NOD mice. This splice variant of CTLA-4, named ligand-independent CTLA-4 (liCTLA-4), lacks exon2 including the MYPPPY motif essential for binding to the costimulatory ligands B7-1 and B7-2. Here we show that liCTLA-4 is expressed as a protein in primary T cells and strongly inhibits T cell responses by binding and dephosphorylating the TcRζ chain. Expression of liCTLA-4, but not full-length CTLA-4 (flCTLA-4), was higher in memory/regulatory T cells from diabetes-resistant NOD congenic mice compared to susceptible NOD mice. These data suggest that increased expression and negative signaling delivered by the liCTLA-4 may regulate development of T cell-mediated autoimmune diseases. [Copyright &y& Elsevier] |
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