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

Dong, Lichun and Li, Penny and Oenema, Tjitske and McClurkan, Christopher L and Koelle, David M (2010) Public TCR use by herpes simplex virus-2-specific human CD8 CTLs. Journal of immunology (Baltimore, Md. : 1950), 184 (6). pp. 3063-3071. ISSN 1550-6606

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Article URL: http://www.jimmunol.org/cgi/content/full/184/6/306...

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.

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above for the first 12 months following publication.
DOI: 10.4049/jimmunol.0903622
PubMed ID: 20139278
NIHMSID: NIHMS192073
PMCID: PMC2863070
Grant Numbers: R01 AI050132-05, P01 AI030731-19
Keywords or MeSH Headings: * Amino Acid Sequence * Antigen-Presenting Cells/immunology * Antigen-Presenting Cells/metabolism * Antigen-Presenting Cells/virology * CD8-Positive T-Lymphocytes/immunology * CD8-Positive T-Lymphocytes/secretion * CD8-Positive T-Lymphocytes/virology * Cell Line, Transformed * Clone Cells * Cytotoxicity Tests, Immunologic/methods * Epitopes, T-Lymphocyte/biosynthesis * Epitopes, T-Lymphocyte/genetics * Epitopes, T-Lymphocyte/immunology* * Genes, T-Cell Receptor alpha/immunology* * Genes, T-Cell Receptor beta/immunology* * HLA-B Antigens/biosynthesis * HLA-B Antigens/genetics * HLA-B Antigens/immunology * Herpesvirus 2, Human/immunology* * Humans * Immunoglobulin Variable Region/biosynthesis * Immunoglobulin Variable Region/genetics * Interferon-gamma/secretion * Molecular Sequence Data * T-Lymphocytes, Cytotoxic/immunology* * T-Lymphocytes, Cytotoxic/secretion * T-Lymphocytes, Cytotoxic/virology* * Virus Latency/immunology
Depositing User: Library Staff
Date Deposited: 31 Mar 2010 20:37
Last Modified: 07 May 2010 16:27
URI: http://authors.fhcrc.org/id/eprint/418

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