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Defining the herpes simplex virus-specific CD8+ T cell repertoire in C57BL/6 mice.

TitleDefining the herpes simplex virus-specific CD8+ T cell repertoire in C57BL/6 mice.
Publication TypeJournal Article
Year of Publication2011
AuthorsSt Leger AJ, Peters B, Sidney J, Sette A, Hendricks RL
JournalJ Immunol
Volume186
Issue7
Pagination3927-33
Date Published2011 Apr 1
ISSN1550-6606
KeywordsAcute Disease, Animals, CD8-Positive T-Lymphocytes, Cell Line, Cells, Cultured, Epitopes, T-Lymphocyte, Female, Herpes Simplex, Herpesvirus 1, Human, Immunodominant Epitopes, Keratitis, Herpetic, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, Trigeminal Ganglion, Virus Latency
Abstract

<p>HSV type 1 (HSV-1) expresses its genes sequentially as immediate early (α), early (β), leaky late (γ1), and true late (γ2), where viral DNA synthesis is an absolute prerequisite only for γ2 gene expression. The γ1 protein glycoprotein B (gB) contains a strongly immunodominant CD8(+) T cell epitope (gB(498-505)) that is recognized by 50% of both the CD8(+) effector T cells in acutely infected trigeminal ganglia (TG) and the CD8(+) memory T cells in latently infected TG. Of 376 predicted HSV-1 CD8(+) T cell epitopes in C57BL/6 mice, 19 (gB(498-505) and 18 subdominant epitopes) stimulated CD8(+) T cells in the spleens and TG of HSV-1 acutely infected mice. These 19 epitopes identified virtually all CD8(+) T cells in the infected TG that represent all or the vast majority of the HSV-specific CD8(+) TCR repertoire. Only 11 of ∼84 HSV-1 proteins are recognized by CD8(+) T cells, and most (∼80%) are expressed before viral DNA synthesis. Neither the immunodominance of gB(498-505) nor the dominance hierarchy of the subdominant epitopes is due solely to MHC or TCR affinity. We conclude that the vast majority of CD8(+) T cells in HSV-1 acutely infected TG are HSV specific, that HSV-1 β and γ1 proteins that are expressed before viral DNA synthesis are favored targets of CD8(+) T cells, and that dominance within the TCR repertoire is likely due to the frequency or expansion and survival characteristics of CD8(+) T cell precursors.</p>

DOI10.4049/jimmunol.1003735
Alternate JournalJ. Immunol.
Citation KeyCK99
PubMed ID21357536
PubMed Central IDPMC3308013
Grant ListP30 EY008098 / EY / NEI NIH HHS / United States
P30 EY008098-21 / EY / NEI NIH HHS / United States
P30 EY008098-22 / EY / NEI NIH HHS / United States
P30 EY008098-23 / EY / NEI NIH HHS / United States
P30 EY008098-24 / EY / NEI NIH HHS / United States
P30-EY08098 / EY / NEI NIH HHS / United States
R01 EY005945 / EY / NEI NIH HHS / United States
R01 EY005945-24 / EY / NEI NIH HHS / United States
R01 EY005945-25 / EY / NEI NIH HHS / United States
R01 EY005945-26 / EY / NEI NIH HHS / United States
R01 EY005945-27 / EY / NEI NIH HHS / United States
R01-EY005945 / EY / NEI NIH HHS / United States
T32-EY017271 / EY / NEI NIH HHS / United States