Altered peptide ligand-induced partial T cell activation: molecular mechanisms and role in T cell biology.
The elucidation of the phenomena of T cell antagonism and partial activation by altered peptide ligands has necessitated a revision in the traditional concepts of TCR recognition of antigen and subsequent signal transduction. Whereas previous models supported a single ligand specificity for any particular T cell, many studies using analogs of immunogenic peptides have now demonstrated a flexibility in this recognition. Moreover, interaction with such altered peptide ligands can result in dramatically different phenotypes of the T cells, ranging from inducing selective stimulatory functions to completely turning off their functional capacity. Investigations of the biochemical basis leading to these phenotypes have shown that altered peptide ligands can induce a qualitatively different pattern of signal transduction events than does any concentration of the native ligand. Such observations imply that several signaling modules are directly linked to the TCR/CD3 complex and that they can be dissociated from each other as a direct result of the nature of the ligand bound. Interestingly, many in vivo models of T cell activation are compatible with a selective signaling model, and several studies have shown that peptide analogs can play a role in various T cell biologic phenomena. These data strongly suggest that naturally occurring altered peptide ligands for any TCR exist in the repertoire of self-peptides or, in nature, derived from pathogens, and recent reports provide compelling evidence that this is indeed the case. The concept of altered peptide ligands, their effects on T cell signaling, the hypothesized mechanisms by which they exert their effects, and their possible roles in shaping the T cell immune response are the scope of this review.
Sloan-Lancaster
J
J
Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Allen
P M
PM
D000818:Animals; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects*; D010455:Peptides / Q000276:immunology* / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D008024:Ligands; D010455:Peptides