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. 1995 Nov 1;182(5):1327–1336. doi: 10.1084/jem.182.5.1327

Genetic basis for T cell recognition of a major histocompatibility complex class II-restricted neo-self peptide

PMCID: PMC2192186  PMID: 7595203

Abstract

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 S1 (HA Tg mice) mediate negative selection of PR8 S1-specific T cells, but respond to immunization with a virus containing a closely related analogue, S1(K113). Sequence analysis of S1(K113)-specific T cell receptors (TCR) from nontransgenic mice revealed a dominant TCR clonotype that cross- reacts with PR8 S1. 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 V alpha/V beta pairing to evade negative selection by the S1 self peptide were identified. The remaining S1(K113)-specific TCRs from HA Tg mice were highly diverse; 13 of 15 S1(K113)-specific TCRs from HA Tg mice used unique V alpha/V beta pairings. Thus, tolerance to PR8 S1 as a self peptide does not limit the diversity of the T cell response to S1(K113).

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Selected References

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