title: Genetic basis for T cell recognition of a major histocompatibility complex class II-restricted neo-self peptide.
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).
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Cerasoli
authors.forename: M P
authors.initials: MP
authors.lastname: Riley
authors.forename: F F
authors.initials: FF
authors.lastname: Shih
authors.forename: A J
authors.initials: AJ
authors.lastname: Caton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016415:Sequence Alignment; D017385:Sequence Homology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D001324:Autoantigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins