Self-reactive T cell hybridomas and tolerance. Same range of antigen dose dependence but higher numbers of self-reactive T cell hybridomas from mice in which self-tolerance has been broken by antiserum treatment.

Abstract

Mechanisms of self-tolerance of 4-hydroxyphenylpyruvate dioxygenase (HPPD) are explored. It is well established that negative selection based on TCR affinity occurs in the thymus. We have investigated the frequency with which self-reactive T cell hybridomas can be obtained in relation to self-tolerance. Mice immunized with the self-form of HPPD gave rise to T cell hybridomas that were able to recognize self-protein and a synthetic peptide representing the T cell epitope, at higher Ag concentration than was necessary for recognition of allo-protein. The efficiency of negative selection was then reduced by treating neonatal mice with anti-HPPD antiserum. This reduced T cell tolerance of the self-protein, as judged by in vitro proliferation, and enabled self-reactive T cell hybridomas to be generated at a higher frequency. However, the Ag concentration requirements of these hybridomas for the self-protein and the self-peptide remained unaltered. The possibility that these findings reflect an auxiliary mechanism of self-tolerance based on frequencies of self-reactive T cells is discussed.