Abstract

T-cell recognition and activation occurs within a specialized area of contact known as the immunologic synapse, localized to areas of glycolipid-enriched membrane microdomains. Within this area, T-cell activation is dependent not only upon specific recognition of peptide antigen embedded within molecules of the major histocompatibility complex, but also on a variety of costimulatory receptors and interactions. Engagement of T-cell receptor (TCR) with antigen alone will induce T-cell unresponsiveness; ligation of the coreceptor CD28 will prevent the induction of unresponsiveness. Novel costimulatory molecules belonging to both the CD28 and TNF/TNFR superfamilies have recently been identified. These receptors appear to act at different stages of T-cell differentiation and activation, have been shown to play a role in promoting different T-cell effector functions, and are important for B-cell differentiation and function.

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