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.