T-cell recognition and activation occurs within a specialized area of conta
ct known as the immunologic synapse, localized to areas of glycolipid-enric
hed membrane microdomains. Within this area, T-cell activation is dependent
not only upon specific recognition of peptide antigen embedded within mole
cules of the major histocompatibility complex, but also on a variety of cos
timulatory receptors and interactions. Engagement of T-cell receptor (TCR)
with antigen alone will induce T-cell unresponsiveness; ligation of the cor
eceptor CD28 will prevent the induction of unresponsiveness. Novel costimul
atory 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 i
n promoting different T-cell effector functions, and are important for B-ce
ll differentiation and function. (C) 2001 Lippincott Williams & Wilkins, In
c.