Pept ide By Douglas

We have analyzed the genetic basis for T cell recognition of an endogenous major histocompatibility complex class II-restricted self peptide. Transgenic mice expressing the influenza virus PR8 hemagglutinin I-Ed-restricted determinant $1 (HA Tg mice) mediate negative selection ofPR8 Sl-specific T cells, but respond to immunization with a virus containing a closely related analogue, $1(Kl13). Sequence analysis of Sl(K113)-specific T cell receptors (TCR) from nontransgenic mice revealed a dominant TCR clonotype that cross-reacts with PR8 $1. This clonotype is eliminated by negative selection in HA Tg mice; nonetheless, modified versions of this TCR that used altered junctional sequences and a novel VoL/V[3 pairing to evade negative selection by the $1 self peptide were identified. The remaining S1(K113)-specific TCRs from HA Tg mice were highly diverse; 13 of 15 $1 (K113)-specific TCRs from HA Tg mice used unique Vow/V[3 pairings. Thus, tolerance to PR8 $1 as a selfpeptide does not limit the diversity of the T cell response to SI(K113).