title: Virus infection expands a biased subset of T cells that bind tetrameric class I peptide complexes.
abstract: We have used a TCR beta-chain transgenic mouse to examine the relationship between the ability of a T cell to bind soluble class I-peptide complexes and its response to antigenic stimulation in vivo. T cells from gBT-I.3beta TCR beta-chain transgenic mice preferentially carried TCR alpha-chains bearing the same Valpha2 V region as found in the parent receptor specific for an immunodominant HSV-1 gB-peptide. Furthermore, CD8(+) T cells from these mice bound K(b)-gB tetrameric complexes with relatively high frequency, and most of these cells contained a Valpha2 TCR alpha-chain. Detailed sequence analysis of the tetramer-binding peripheral T cells showed that this was a heterogenous population expressing TCR with only partial sequence similarity to the parent receptor, which took the form of preferential inclusion of the parental Jalpha16 element. Infection with HSV-1, however, selected a subset of tetramer-positive T cells. This was based on the emergence of a co-dominant Jalpha usage and selection of a restricted CDR3alpha length. Therefore, the ability to bind soluble MHC-peptide complexes does not always correlate with the ability of a T cell to respond to its cognate antigen after in vivo stimulation.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Coles
authors.forename: Claerwen M
authors.initials: CM
authors.lastname: Jones
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D001704:Biopolymers; D022801:Complementarity Determining Regions / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D006561:Herpes Simplex / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D018139:Simplexvirus / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D001704:Biopolymers; D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016056:Immunodominant Epitopes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus