Cutting edge: positive selection induced by a self-peptide with TCR antagonist activity.
Antagonist-like engagement of the TCR has been proposed to induce T cell selection in the thymus. However, no natural TCR ligand with TCR antagonist activity is presently known. Using a combination of bioinformatics and functional testing we identified the first self-peptide that can both deliver antagonist-like signals and promote T cell selection in the thymus. The peptide is presented by appropriate MHC class I molecules in vivo. Thus, endogenous antagonist peptides exist and may be involved in TCR repertoire selection.
Santori
F R
FR
Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Brown
S M
SM
Lu
Y
Y
Neubert
T A
TA
Vukmanovic
S
S
D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D005260:Female; D005333:Fetus; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001324:Autoantigens; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell