title: Diversity of the CD8+ T cell repertoire elicited against an immunodominant epitope does not depend on the context of infection.
abstract: The diversity of the pathogen-specific T cell repertoire is believed to be important in allowing recognition of different pathogen epitopes and their variants and thereby reducing the opportunities for mutation-driven pathogen escape. However, the extent to which the TCR repertoire can be manipulated by different vaccine strategies so as to obtain broad diversity and optimal protection is incompletely understood. We have investigated the influence of the infectious/inflammatory context on the TCR diversity of the CD8(+) T cell response specific for the immunodominant epitope in C57BL/6 mice, derived from glycoprotein B of HSV-1. To that effect, we compared TCR V segment utilization, CDR3 length, and sequence diversity of the response to natural HSV-1 infection with those elicited by either Listeria monocytogenes or vaccinia virus expressing the immunodominant epitope in C57BL/6 mice. We demonstrate that although the type of infection in which the epitope was encountered can influence the magnitude of the CD8(+) T cell responses, TCR beta-chain repertoires did not significantly differ among the three infections. These results suggest that widely different live vaccine vectors may have little impact upon the diversity of the induced CTL response, which has important implications for the design of live CTL vaccine strategies against acute and chronic infections.
authors.affiliation: Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724 and the BIO-5 Institute, University of Arizona, Tucson,AZ 85719.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Rudd
authors.affiliation: Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.affiliation: Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724 and the BIO-5 Institute, University of Arizona, Tucson,AZ 85719.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Smithey
authors.affiliation: Department of Pediatrics, Center for Infectious Disease and Microbiology Translational Research, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
authors.affiliation: Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia.
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.affiliation: Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724 and the BIO-5 Institute, University of Arizona, Tucson,AZ 85719.
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Zugich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D016503:Drug Delivery Systems; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D014615:Vaccinia / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D022301:Herpes Simplex Virus Vaccines; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus