SELF-TOLERANCE TO T-CELL RECEPTOR V-BETA SEQUENCES

T cell tolerance to self is achieved by deletion or inactivation of cl ones recognizing peptides of self proteins presented by major histocom patibility complex molecules. A considerable fraction of self proteins accessible to the immune system is contributed by the system itself, for example, the receptors used for antigen recognition (antibodies an d T cell receptors [TCRs]). Thus far, it has remained unclear, whether antigen receptors are subject to self tolerance, or on contrary, enga ge into network interactions implying immunity rather than tolerance. In this study, we demonstrate self tolerance to synthetic peptides cor responding to the first hypervariable region of the V beta 8.1 and V b eta 8.2 TCR proteins. We also show that the tolerogenic synthetic pept ide corresponds to a fragment produced by processing of the V beta pro tein, and conversely, that a V beta peptide not produced by processing is also not subject to self tolerance. Thus, the rules of tolerance s eem to apply to antigen receptors, at least to their germline-encoded portions, in a similar fashion as to other self proteins. This finding has important implications for studies of natural and artificially in duced immune networks.