RGD Reference Report - Negative regulation of T cell receptor-lipid raft interaction by cytotoxic T lymphocyte-associated antigen 4. - Rat Genome Database

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Negative regulation of T cell receptor-lipid raft interaction by cytotoxic T lymphocyte-associated antigen 4.

Authors: Chikuma, S  Imboden, JB  Bluestone, JA 
Citation: Chikuma S, etal., J Exp Med 2003 Jan 6;197(1):129-35.
RGD ID: 1358537
Pubmed: PMID:12515820   (View Abstract at PubMed)
PMCID: PMC2193802   (View Article at PubMed Central)

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an essential negative regulator of T cell activation. Recent evidence suggests that CTLA-4 association with the immunological synapse during contact with antigen-presenting cells is important for its inhibitory function. In the present study, we observed a direct interaction of CTLA-4 with the phosphorylated form of T cell receptor (TCR)zeta within the glycolipid-enriched microdomains associated with the T cell signaling complex. In this setting, CTLA-4 regulated the accumulation/retention of TCRzeta in the signaling complex, as the lipid raft fractions from CTLA-4KO T cells contained significantly higher amounts of the TCR components when compared with wild-type littermates. In contrast, coligation of CTLA-4 with the TCR during T cell activation selectively decreased the amount of TCRzeta that accumulated in the rafts. These results suggest that CTLA-4 functions to regulate T cell signaling by controlling TCR accumulation and/or retention within this a critical component of the immunological synapse.

Objects referenced in this article
Gene Ctla4 cytotoxic T-lymphocyte-associated protein 4 Rattus norvegicus

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