Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor.
The study of immunodominance within microbe-specific CD8 T cell responses has been challenging. We used a previously undescribed approach to create unbiased panels of CD8 cytotoxic T lymphocyte clones specific for herpes simplex virus type 2, a pathogen with a complex genome encoding at least 85 polypeptides. Circulating herpes simplex virus type 2-specific cells were enriched and cloned after sorting for expression of the skin homing-associated receptor, cutaneous lymphocyte-associated antigen, bypassing restimulation with antigen. The specificity of the resultant cytotoxic clones was determined. Clonal frequencies were compared with each other and with the total number of cytotoxic clones. For each subject within the homing receptor-positive compartment, the CD8 cytotoxic response was dominated by T cells specific for only a few peptides. Previously undescribed antigens and epitopes in viral tegument, capsid, or scaffold proteins were immunodominant in some subjects. Clone enumeration analyses were confirmed in some subjects with dominance studies by using herpes simplex mutants, vaccinia recombinants, and/or enzyme-linked immune spots. We conclude that among circulating cells expressing a homing-associated receptor, during chronic herpes type 2 infection, the CD8 T cell response becomes quite focused despite the presence of many potential antigenic peptides.
Koelle
David M
DM
Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA. viralimm@u.washington.edu
Liu
Zhi
Z
McClurkan
Christopher L
CL
Cevallos
Randal C
RC
Vieira
Jeffrey
J
Hosken
Nancy A
NA
Meseda
Clement A
CA
Snow
Devon C
DC
Wald
Anna
A
Corey
Lawrence
L
D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015234:HLA-A Antigens / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008212:Lymphocyte Depletion; D016366:Open Reading Frames; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D015234:HLA-A Antigens; D016056:Immunodominant Epitopes; D016201:Receptors, Lymphocyte Homing