title: Naive T cell repertoire skewing in HLA-A2 individuals by a specialized rearrangement mechanism results in public memory clonotypes.
abstract: How the naive T cell repertoire arises and forms the memory repertoire is still poorly understood. This relationship was analyzed by taking advantage of the focused TCR usage in HLA-A2-restricted CD8 memory T cell responses to influenza M1(58-66). We analyzed rearranged BV19 genes from CD8 single-positive thymocytes, a surrogate for the naive repertoire, from 10 HLA-A2 individuals. CDR3 amino acid sequences associated with response to influenza were observed at higher frequencies than expected by chance, an indicator of preselection. We propose that a rearrangement mechanism involving long P-nucleotide addition from the J2.7 region explains part of this increase. Special rearrangement mechanisms can result in identical T cells in different individuals, referred to as public responses. Indeed, the rearrangements utilizing long P nucleotide additions were commonly observed in the response to the M1(58-66) epitope in 30 HLA-A2 middle-aged adults. Thus, in addition to negative and positive selection, special rearrangement mechanisms may influence the composition of the naive repertoire, resulting in more robust responses to a pathogen in some individuals.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Yassai
authors.forename: Dmitry
authors.initials: D
authors.lastname: Bosenko
authors.forename: Melissa
authors.initials: M
authors.lastname: Unruh
authors.forename: Gregory
authors.initials: G
authors.lastname: Zacharias
authors.forename: Erica
authors.initials: E
authors.lastname: Reed
authors.forename: Wendy
authors.initials: W
authors.lastname: Demos
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrante
authors.forename: Jack
authors.initials: J
authors.lastname: Gorski
mesh_terms: D000328:Adult; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics*; D008875:Middle Aged; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins