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Decoding Immunodominance of an Antiviral CD8+ T Cell Response
Author(s) -
Kotturi Maya,
Scott Iain,
Wolfe Tom,
Peters Bjoern,
Sidney John,
Herrath Matthias G.,
Buchmeier Michael J.,
Grey Howard,
Sette Alessandro
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.855.3
Subject(s) - immunodominance , epitope , biology , virology , lymphocytic choriomeningitis , cytotoxic t cell , antigen , cd8 , immunology , genetics , in vitro
The primary CD8 + T cell response against lymphocytic choriomeningitis virus (LCMV) infection of C57BL/6J mice is directed against 28 H‐2 b ‐restricted epitopes derived from the glycoprotein, nucleoprotein and RNA polymerase L protein. Within these 28 epitopes a clear immunodominance hierarchy is observed. Some major epitopes dominate the response, while some epitopes are intermediate and others are relatively minor contributors to the overall response. To probe the mechanisms regulating CD8 + T cell immunodominance, we manipulated the number of epitopes seen during acute LCMV infection. Deletion of epitope‐specific responses, either by using a LCMV viral variant lacking 4 major epitopes, or C57BL/6J mice altogether lacking expression of H‐2K b , resulted in an overall decrease of the response, minor compensatory effects, and no detectable responses against new epitopes. Increasing the number of epitopes available for recognition by use of H‐2 b F1 hybrid mice, or delivery of LCMV antigens by recombinant vaccinia virus also did not dramatically alter the immunodominance pattern. These data suggest that immunodominance hierarchy might be intrinsic to the epitope and its antigen of origin. We are currently investigating these issues by directly measuring the hierarchies in MHC binding affinities, the yield of epitope production as a result of cellular processing, and by quantifying the existing naïve T cell repertoire by the use of a sensitive tetramer‐based enrichment method.