T cells are classified as belonging to the αβ or γδ lineage depending on which clonotypic heterodimer is incorporated into their T cell antigen receptor (TCR). Associated with αβ or γδ chains are the ζ homodimer and CD3 heterodimers, which are responsible for transducing signals across the plasma membrane into the cytoplasm, where signaling cascades ensue. The TCR is required for signaling governing such processes as development, differentiation and activation. Loss of any CD3 component leads to a block in αβ T cell development, as the signaling required for successful passage through various checkpoints becomes impaired. In mice, the CD3 subunit requirements for assembly and function of the γδTCR are different from those of the αβTCR. Recently, we have determined that they also differ between mouse and man. In this chapter, we discuss αβ and γδTCR composition and function, the novel assay we developed to determine TCR stoichiometries, and how these discoveries lead to a better understanding of CD3 deficiency phenotypes
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