CD3-DELTA DEFICIENCY ARRESTS DEVELOPMENT OF THE ALPHA-BETA BUT NOT THE GAMMA-DELTA T-CELL LINEAGE

The CD3 complex found associated with the T cell receptor (TCR) is ess ential for signal transduction following TCR engagement. During T cell development, TCR-mediated signalling promotes the transition from one developmental stage to the next and controls whether a thymocyte unde rgoes positive or negative selection, The roles of particular CD3 comp onents in these events remain unclear. Indeed, it is unknown whether t hey have specialized or overlapping roles. However, the multiplicity o f CD3 components and their evolutionary conservation suggest that they serve distinct functions. Here the developmental requirement for the CD3 delta chain is analyzed by generating a mouse line specifically la cking this component (delta-/- mice), Strikingly, CD3 delta is shown t o be differentially required during development. In particular, CD3 de lta is not needed for steps in development mediated by pre-TCR or gamm a delta TCR, but is required for further development of thymocytes exp ressing alpha beta TCR, Absence of CD3 delta specifically blocks the t hymic selection processes that mediate the transition from the double- positive to single-positive stages of development.