The proliferative capacity of individual naive XXXX (+) T cells is amplified by prolonged T cell antigen receptor triggering.

@entity1199 @entity404 @entity6057 @entity2902
Strong antigenic encounter by T cells rapidly induces immunological synapse formation and surface @entity6057 ( @entity6057 ) downregulation. Although surface @entity6057 expression can remain low for several days, T cells can still sustain antigenic signaling. It has been unclear whether prolonged antigenic signaling occurs in the absence of surface @entity6057 replenishment, being maintained by a few "nondownregulatable" surface TCRs that might reside in a synaptosomal structure. Alternatively, the low surface @entity6057 level induced by antigen might represent a dynamic state of expression involving continual surface @entity6057 replenishment, reengagement by antigen, and ongoing downregulation. To resolve this issue, we studied in vivo-generated, dual-specificity primary naive @entity404 (+) T cells. On these cells, antigenic stimulus exclusively downregulated antigen-specific, but not antigen-nonspecific, TCRs. In addition to providing a means to track @entity6057 engagement, this also allowed us to use the antigen nonspecific @entity6057 to track @entity6057 expression in isolation from @entity6057 engagement by antigen. Surface @entity6057 replenishment began within the first day of stimulation, and occurred synchronously with continuous antigen-specific @entity6057 engagement and downregulation. Furthermore, by enhancing @entity2902 expression, extended signaling through surface-replenishing TCRs significantly amplified the number of daughter cells generated by naive @entity404 (+) T cells that had already committed to proliferate. This effect required @entity6057 engagement and could not be substituted for by @entity1199 . These data demonstrate that @entity6057 triggering and consumption can occur over an extended period of time, with a significant impact on the effector responses evoked from naive @entity404 (+) T cells.
