J. Exp. Med., Volume 186, Number 10, November 17, 1997 1775-1779

BRIEF DEFINITIVE REPORT:
Quantitative Contribution of CD4 and CD8 to T Cell Antigen Receptor Serial Triggering

By Antonella Viola,^* Mariolina Salio,^* Loretta Tuosto, Susanne Linkert,^* Oreste Acuto, and Antonio Lanzavecchia^*

From the ^* Basel Institute for Immunology, 4005, Basel, Switzerland; and  Molecular Immunology Unit Institut Pasteur, 75724 Paris Cedex 15, France

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

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