The CD8+ T-cell response to lymphocytic choriomeningitis virus involves the L antigen: uncovering new tricks for an old virus

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of virology Vol. 81; no. 10; p. 4928
Main Authors: Kotturi, Maya F, Peters, Bjoern, Buendia-Laysa, Jr, Fernando, Sidney, John, Oseroff, Carla, Botten, Jason, Grey, Howard, Buchmeier, Michael J, Sette, Alessandro
Format: Journal Article
Language:English
Published: United States 01.05.2007
Subjects:
Animals
Antigens, Viral - immunology
Arenaviridae Infections - immunology
CD8-Positive T-Lymphocytes - immunology
Cytotoxicity, Immunologic
Disease Models, Animal
DNA-Directed RNA Polymerases - immunology
Epitope Mapping
Epitopes, T-Lymphocyte - immunology
Female
Hyaluronan Receptors - analysis
Interferon-gamma - biosynthesis
Lymphocytic choriomeningitis virus - immunology
Mice
Mice, Inbred C57BL
Spleen - virology
Viral Plaque Assay
ISSN:0022-538X
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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-gamma) 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-gamma 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-538X
DOI:10.1128/JVI.02632-06