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

J Exp Med. 1995 Nov 1;182(5):1327-36. doi: 10.1084/jem.182.5.1327.

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).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Autoantigens / immunology*
  • Base Sequence
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral / genetics
  • Hemagglutinins, Viral / immunology*
  • Histocompatibility Antigens Class II / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Molecular Sequence Data
  • Orthomyxoviridae / immunology
  • Peptide Fragments / immunology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / immunology
  • Sequence Alignment
  • Sequence Homology
  • T-Lymphocyte Subsets / immunology*

Substances

  • Antigens, Viral
  • Autoantigens
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral
  • Histocompatibility Antigens Class II
  • I-E-antigen
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins

Associated data

  • GENBANK/U21393
  • GENBANK/U21439
  • GENBANK/U21440
  • GENBANK/U21441
  • GENBANK/U21442
  • GENBANK/U21443
  • GENBANK/U21444
  • GENBANK/U21445
  • GENBANK/U21446
  • GENBANK/U21447
  • GENBANK/U21448
  • GENBANK/U21449
  • GENBANK/U21450
  • GENBANK/U21451
  • GENBANK/U21452
  • GENBANK/U21453
  • GENBANK/U21454
  • GENBANK/U21455
  • GENBANK/U21456
  • GENBANK/U21477
  • GENBANK/U21478
  • GENBANK/U21479
  • GENBANK/U21480
  • GENBANK/U21481