QUANTITATIVE CONTRIBUTION OF CD4 AND CD8 TO T-CELL ANTIGEN RECEPTOR SERIAL TRIGGERING

CD4 and CD8 are drought to function as coreceptors by binding to tile cognate major histocompatibility complex (MHC) molecules recognized by the T cell antigen receptor (TCR) and initiating the signal transduct ion cascade. We report that during T cell-antigen-presenting cell inte raction, triggered TCRs and coreceptors are downregulated and degraded with identical kinetics. This coordinated disappearance takes place w henever the TCR is triggered, even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the cor eceptor-associated Lck to ZAP-70. The interaction of coreceptor and co gnate MHC molecules is dispensable when T cells are stimulated by opti mal ligands, but becomes crucial when suboptimal ligands are used. In the latter case the coreceptor increases the efficiency of TCR trigger ing without changing the activation threshold or the quality of the T cell response.