Public TCR use by herpes simplex virus-2-specific human CD8 CTLs.

Publication Type:

Journal Article

Source:

Journal of immunology (Baltimore, Md. : 1950), Volume 184, Issue 6, p.3063-71 (2010)

Keywords:

2010, Amino Acid Sequence, Antigen-Presenting Cells, CD8-Positive T-Lymphocytes, Cell Line, Transformed, Clone Cells, Cytotoxicity Tests, Immunologic, Epitopes, T-Lymphocyte, Genes, T-Cell Receptor alpha, Genes, T-Cell Receptor beta, Herpesvirus 2, Human, HLA-B Antigens, Humans, Immunoglobulin Variable Region, interferon-gamma, Molecular Sequence Data, T-Lymphocytes, Cytotoxic, Vaccine and Infectious Disease Division, Virus Latency

Abstract:

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.