Public TCR use by herpes simplex virus-2-specific human CD8 CTLs.
Recombination of germline TCR alpha and beta genes generates polypeptide receptors for MHC peptide. Ag exposure during long-term herpes simplex infections may shape the T cell repertoire over time. We investigated the CD8 T cell response to HSV-2 in chronically infected individuals by sequencing the hypervariable regions encoding TCR alpha and beta polypeptides from T cell clones recognizing virion protein 22 aa 49-57, an immunodominant epitope. The most commonly detected TCRBV gene segment, found in four of five subjects and in 12 of 50 independently derived T cell clones, was TCRBV12-4. Nineteen to seventy-two percent of tetramer-binding cells in PBMCs were stained ex vivo with a TCRBV12 mAb. Three alpha-chain and three beta-chain public TCR sequences were shared between individuals. Public heterodimers were also detected. Promiscuous pairing of a specific TCRVA1-1 sequence with several different TCRB polypeptides was observed, implying a dominant structural role for the TCRA chain for these clonotypes. Functional avidity for cytotoxicity and IFN-gamma release was relatively invariant, except for one subject with both high avidity and unique TCR sequences and lower HSV-2 shedding. These data indicate that the CD8 response to a dominant alpha-herpesvirus epitope converges on preferred TCR sequences with relatively constant functional avidity.
Department of Medicine, University of Washington, Seattle, WA 98102, USA.
Lichun
L
Dong
Penny
P
Li
Tjitske
T
Oenema
Christopher L
CL
McClurkan
David M
DM
Koelle
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002461:Cell Line, Transformed; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology*; D019674:Genes, T-Cell Receptor beta / Q000276:immunology*; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015793:HLA-B7 Antigen; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D017735:Virus Latency / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D007135:Immunoglobulin Variable Region; D007371:Interferon-gamma