Molecular analysis of the influences of positive selection, tolerance induction, and antigen presentation on the T cell receptor repertoire

Abstract

Immunization ofboth B10.A and B10.S(9R) mice with pigeon cytochrome c (pcc) elicits T cells capable ofproliferating to pcc presented on I-E major histocompatibility complex (MHC) molecules. The T cell receptor (TCR) repertoire used by pcc-specific T cells from these two strains is markedly different, even for T cells recognizing very similar antigen/MHC complexes. Our current studies have been directed toward explaining this differential expression between MHC congenic strains of TCR gene elements capable of recognizing similar ligands. Analysis of the TCR repertoire of pcc-specific T cells from F1[B10.A x B10.S (9R)] → parent radiation chimeras has demonstrated that much ofthis difference is a result of the positive selection ofT cells for MHC restriction specificity. Further analysis of T cell lines from Fl mice and from radiation chimeras stimulated in vitro with pcc on both B10.A and B10.S(9R) antigen-presenting cells has provided clear-cut examples of the influence of positive selection, tolerance induction and of both in vivo and in vitro antigen presentation on the shaping of the TCR repertoire for a protein antigen. This is the first molecular analysis ofhow positive selection, tolerance induction, and antigen presentation can combine to mold the TCR repertoire. © 1990, Rockefeller University Press., All rights reserved.