Context
"Negative selection" or deletion of potentially autoreactive immature thymocytes occurs by apoptosis of cells bearing an antigen receptor with high affinity for self major histocompatibility complex (MHC). The molecular requirements for thymocyte apoptosis induced during negative selection are beginning to be defined. Functional defects in the signaling cascade downstream of the T-cell antigen receptor (e.g. mutations in CD3?, the adaptors Grb2 and Gads, the kinases Itk and Rlk) have already been associated with impaired deletion. In contrast, and perhaps surprisingly, proteins known to play a role in apoptosis induced by "death receptor" ligation (e.g. CD95, FADD, Caspase-8) have limited roles in thymocyte deletion. The present paper is, therefore, among the first to show that mutation of a protein within the machinery of death influences thymocyte apoptosis.