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
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, Viral / genetics
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Antigens, Viral / immunology*
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Autoantigens / immunology*
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Base Sequence
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Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
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Hemagglutinin Glycoproteins, Influenza Virus
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Hemagglutinins, Viral / genetics
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Hemagglutinins, Viral / immunology*
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Histocompatibility Antigens Class II / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Molecular Sequence Data
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Orthomyxoviridae / immunology
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Peptide Fragments / immunology*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology*
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Recombinant Fusion Proteins / immunology
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Sequence Alignment
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Sequence Homology
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T-Lymphocyte Subsets / immunology*
Substances
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Antigens, Viral
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Autoantigens
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Hemagglutinin Glycoproteins, Influenza Virus
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Hemagglutinins, Viral
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Histocompatibility Antigens Class II
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I-E-antigen
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
Associated data
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GENBANK/U21393
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GENBANK/U21439
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GENBANK/U21440
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GENBANK/U21441
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GENBANK/U21442
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GENBANK/U21443
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GENBANK/U21444
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GENBANK/U21445
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GENBANK/U21446
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GENBANK/U21447
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GENBANK/U21448
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GENBANK/U21449
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GENBANK/U21450
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GENBANK/U21451
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GENBANK/U21452
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GENBANK/U21453
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GENBANK/U21454
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GENBANK/U21455
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GENBANK/U21456
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GENBANK/U21477
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GENBANK/U21478
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GENBANK/U21479
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GENBANK/U21480
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GENBANK/U21481