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Cutting Edge: Positive Selection Induced by a Self-Peptide with TCR Antagonist Activity¹

Fabio R. Santori^*, Stuart M. Brown, Yun Lu, Thomas A. Neubert and Stanislav Vukmanovi^2,*

^* Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Cancer Center, Department of Cell Biology, Skirball Institute of Biomolecular Medicine, Department of Pharmacology, New York University School of Medicine, New York, NY 10016

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.

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