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, 16 (1), 23-35

Cytotoxic T Lymphocyte antigen-4 Accumulation in the Immunological Synapse Is Regulated by TCR Signal Strength

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Cytotoxic T Lymphocyte antigen-4 Accumulation in the Immunological Synapse Is Regulated by TCR Signal Strength

Jackson G Egen et al. Immunity.

Abstract

CD28 and CTLA-4 engagement with B7 expressed by APCs generates critical regulatory signals for T cell activation. CD28 is expressed on the T cell surface and enhances T cell expansion, while CTLA-4 localizes primarily to an intracellular compartment and inhibits T cell proliferation. We demonstrate that CTLA-4 has several unique trafficking properties that may regulate its ability to attenuate a T cell response. Importantly, accumulation of CTLA-4 at the immunological synapse is proportional to the strength of the TCR signal, suggesting that cells receiving stronger stimuli are more susceptible to CTLA-4-mediated inhibition. This may represent a novel feedback control mechanism in which a stimulatory signal regulates the recruitment of an inhibitory receptor to a functionally relevant site on the cell surface.

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