In:
Journal of Virology, American Society for Microbiology, Vol. 81, No. 10 ( 2007-05-15), p. 4928-4940
Abstract:
CD8 + T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2 b mice. Although antigen-specific responses against LCMV infection are well studied, we found that a significant fraction of the CD8 + CD44 hi T-cell response to LCMV in H-2 b mice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCMV proteome for gamma interferon (IFN-γ) induction from CD8 + T cells derived from LCMV-infected H-2 b mice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8 + CD44 hi response. Thus, bystander T-cell activation does not contribute appreciably to the CD8 + CD44 hi pool. Strikingly, 15 of the 19 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCMV infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8 + T cells, whereas IFN-γ production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCMV-specific CD8 + T-cell response is more complex than previously appreciated.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.02632-06
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2007
detail.hit.zdb_id:
1495529-5
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