J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/02/641/12 $2.00
Volume 185, Number 4, February 17, 1997 641-652

Requirements for Peptide-induced T Cell Receptor Downregulation on Naive CD8⁺ T Cells

By Zeling Cai, Hidehiro Kishimoto,^* Anders Brunmark, Michael R. Jackson, Per A. Peterson, and Jonathan Sprent^*

From the ^* Department of Immunology, IMM4, The Scripps Research Institute, La Jolla, California 92037; and  R.W.  Johnson Pharmaceutical Research Institute, San Diego, California 92121

The requirements for inducing downregulation of / T cell receptor (TCR) molecules on naive major histocompatibility complex class I-restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling.

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