@article {542601,
	title = {An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells.},
	journal = {Immunity},
	volume = {20},
	number = {5},
	year = {2004},
	month = {2004 May},
	pages = {563-75},
	abstract = {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 TcRzeta 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.},
	keywords = {Amino Acid Sequence, Animals, Antigens, CD, Antigens, CD80, Antigens, Differentiation, Autoimmune Diseases, Blotting, Western, Cloning, Molecular, CTLA-4 Antigen, Female, Flow Cytometry, Humans, Membrane Proteins, Mice, Mice, Inbred NOD, Molecular Sequence Data, Receptors, Antigen, T-Cell, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Signal Transduction, T-Lymphocytes},
	issn = {1074-7613},
	author = {Vijayakrishnan, Lalitha and Slavik, Jacqueline M and Ill{\'e}s, Zsolt and Greenwald, Rebecca J and Rainbow, Dan and Greve, Bernhard and Peterson, Laurence B and Hafler, David A and Freeman, Gordon J and Sharpe, Arlene H and Wicker, Linda S and Kuchroo, Vijay K}
}
