title: Public T cell receptor beta-chains are not advantaged during positive selection.
abstract: Studies of human and murine T cells have shown that public TCR beta-chain rearrangements can dominate the Ag-specific and naive repertoires of distinct individuals. We show that mouse T cells responding to the minor histocompatibility Ag HYDbSmcy share an invariant Vbeta8.2-Jbeta2.3 TCR gene rearrangement. The dominance of this rearrangement shows that it successfully negotiated thymic selection and was highly favored during clonal expansion in all animals examined. We hypothesized that such beta-chains are advantaged during thymic and/or peripheral selection and, as a result, may be over-represented in the naive repertoire. A sequencing study was undertaken to examine the diversity of Vbeta8.2-Jbeta2.3 CDR3 loops from naive T cell repertoires of multiple mice. Public TCR beta-chain sequences were identified across different repertoires and MHC haplotypes. To determine whether such public beta-chains are advantaged during thymic selection, individual chains were followed through T cell development in a series of novel bone marrow competition chimeras. We demonstrate that beta-chains were positively selected with similar efficiency regardless of CDR3 loop sequence. Therefore, the establishment and maintenance of public beta-chains in the periphery is predominantly controlled by post-thymic events through modification of the primary, thymus-derived TCR repertoire.
authors.affiliation: Department of Immunology, Hammersmith Hospital, Imperial College London, London, United Kingdom. a.furmanski@ich.ucl.ac.uk
authors.forename: Anna L
authors.initials: AL
authors.lastname: Furmanski
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferreira
authors.forename: Istvan
authors.initials: I
authors.lastname: Bartok
authors.forename: Sofia
authors.initials: S
authors.lastname: Dimakou
authors.forename: Jason
authors.initials: J
authors.lastname: Rice
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
authors.forename: Maggie M
authors.initials: MM
authors.lastname: Millrain
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Simpson
authors.forename: Julian
authors.initials: J
authors.lastname: Dyson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000378:metabolism; D056466:Histone Demethylases; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011506:Proteins / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012641:Selection, Genetic; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D015778:Minor Histocompatibility Antigens
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D049452:Green Fluorescent Proteins; D056466:Histone Demethylases; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C490659:Kdm5d protein, mouse; D015778:Minor Histocompatibility Antigens