The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
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Published 6 January 2003. doi:10.1084/jem.20021646
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© Rockefeller University Press, 0022-1007/2003/1/129 $5.00
The Journal of Experimental Medicine, Volume 197, Number 1, 129-135

Brief Definitive Report

Negative Regulation of T Cell Receptor–Lipid Raft Interaction by Cytotoxic T Lymphocyte–associated Antigen 4

Shunsuke Chikuma1,2, John B. Imboden2 and Jeffrey A. Bluestone1,2

1 Diabetes Center, University of California at San Francisco, San Francisco, CA 94143
2 Department of Medicine, University of California at San Francisco, San Francisco, CA 94143

Address correspondence to Dr. Jeffrey A. Bluestone, Diabetes Center, University of California, 513 Parnassus Ave., Box 0540, San Francisco, CA 94143-0540. Phone: 415-514-1683; Fax: 415-564-5813; E-mail: jbluest{at}diabetes.ucsf.edu

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 TCR{zeta} 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 TCR{zeta} 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.

Key Words: costimulation • T cells • GEM • immunological synapse • negative signal


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