REQUIREMENTS FOR PEPTIDE-INDUCED T-CELL RECEPTOR DOWN-REGULATION ON NAIVE CD8(-CELLS() T)

The requirements for inducing downregulation of alpha/beta T cell rece ptor (TCR) molecules on naive major histocompatibility complex class I -restricted T cells was investigated with 2C TCR transgenic mice and d efined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression o n the responder cells and was heavily dependent upon costimulation pro vided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). Thes e stringent requirements did not apply to TCR downregulation. Thus, TC R downregulation seemed to depend solely on TCR/peptide/interaction an d did not require either CD8 or B7-1 expression; ICAM-1 potentiated TC R downregulation, but only with limiting doses of peptides. TCR downre gulation was most prominent with high affinity peptides and appeared t o be neither obligatory nor sufficient for T cell activation. In marke d contrast to T cell activation, TCR downregulation was resistant to v arious metabolic inhibitors. The biological significance of TCR downre gulation is unclear, but could be a device for protecting T cells agai nst excessive signaling.