Epitopes described in "Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope."

Article Authors:Alex T Chen; Markus Cornberg; Stephanie Gras; Carole Guillonneau; Jamie Rossjohn; Andrew Trees; Sebastien Emonet; Juan C de la Torre; Raymond M Welsh; Liisa K Selin
Article Title:Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope.
Reference Detail
Reference ID:1023056
Abstract:T cell cross-reactivity between different strains of the same virus, between different members of the same virus group, and even between unrelated viruses is a common occurrence. We questioned here how an intervening infection with a virus containing a sub-dominant cross-reactive T cell epitope would affect protective immunity to a previously encountered virus. Pichinde virus (PV) and lymphocytic choriomeningitis virus (LCMV) encode subdominant cross-reactive NP₂₀₅₋₂₁₂ CD8 T cell epitopes sharing 6 of 8 amino acids, differing only in the MHC anchoring regions. These pMHC epitopes induce cross-reactive but non-identical T cell receptor (TCR) repertoires, and structural studies showed that the differing anchoring amino acids altered the conformation of the MHC landscape presented to the TCR. PV-immune mice receiving an intervening infection with wild type but not NP205-mutant LCMV developed severe immunopathology in the form of acute fatty necrosis on re-challenge with PV, and this pathology could be predicted by the ratio of NP205-specific to the normally immunodominant PV NP₃₈₋₄₅-specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses.
Affiliations:Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Reference Type:Literature
PubMed ID:22536152
Journal:PLoS Pathog
Journal Volume:8
Article Pages:e1002633
Journal ISSN:1553-7374
Article Chemical List:Epitopes, T-Lymphocyte;Receptors, Antigen, T-Cell;Viral Proteins
Article MeSH List:Animals; CD8-Positive T-Lymphocytes(immunology; metabolism); Cross Reactions(immunology); Epitopes, T-Lymphocyte(genetics; immunology); Lymphocytic Choriomeningitis(genetics; immunology); Lymphocytic choriomeningitis virus; Male; Mice; Mutation; Pichinde virus(genetics; immunology); Receptors, Antigen, T-Cell(genetics; immunology); Viral Proteins(genetics; immunology)
Curation Last Updated:2015-07-30 20:45:16