A Redundant Role of the CD3#gamma#-Immunoreceptor Tyrosine-Based Activation Motif in Matue T Cell Function

摘要

At least four different CD3 polypeptide chains are contained within the mature TCR complex, each encompassing one (CD3'Y CD36, and CD3E) or three (CD3#zeta#) immunoreceptor tyrosine-based activation motifs (ITAMs) within their cytoplasmic domains Why so many ITAMs are required is unresolved: it has been speculated that the different ITAMs function in signal specification but they may also serve in signal amplification. Because the CD31; chains do not contribute unique signaling functions to the TCR and because the IT AMs of the CD3-1'6E module alone can endow the TCR with normal signaling capacity, it thus become! important to examine how the CD31'-, 6-, and E-ITAMs regulate TCR signaling. We here report on the role of the CD31' chaill and the CD31'-ITAM in peripheral T cell activation and differentiation to effector function. All T cell responses were reduced 01 abrogated in T cells derived from CD31' nulI-mutant mice, probably because of decreased expression levels of the mature TCR complex lacking CD31'. Consistent with this explanation, T cell responses proceed undisturbed in the absence of afunctional CD31'-ITAM. Loss of integrity of the CD31'-ITAM only slightly impaired the regulation of expression of activation markers, suggesting a quantitative contribution of the CD31'-IT AM in this process. Nevertheless, the induction of an in vivo T cell responsf in influenza A virus-infected CD31'-ITAM-deficient mice proceeds normally. Therefore, if ITAMs can function in signal specifi- cation, it is likely that either the CD36 and/or the CD3E chains endow the TCR with qualitatively unique signaling functions. The Journal ~f ImmunoloJ!V. 2001. 166: 2576-2588.