Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T cells.
The requirements for inducing downregulation of alpha/beta 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.
Cai
Z
Z
Department of Immunology, IMM4, The Scripps Research Institute, La Jolla, California 92037, USA.
Kishimoto
H
H
Brunmark
A
A
Jackson
M R
MR
Peterson
P A
PA
Sprent
J
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D004705:Endocytosis; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*
D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018799:Intercellular Adhesion Molecule-1