Title
Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope
PubMed ID
22536152
UMMS Affiliation
Department of Pathology
Date
4-19-2012
Document Type
Article
Subjects
Animals; CD8-Positive T-Lymphocytes; Cross Reactions; Epitopes, T-Lymphocyte; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Mice; Mutation; Pichinde virus; Receptors, Antigen, T-Cell; Viral Proteins
Disciplines
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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 NP(2)(0)(5)(-)(2)(1)(2) 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 NP(3)(8)(-)(4)(5)-specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses.
Comments
Citation: Chen AT, Cornberg M, Gras S, Guillonneau C, Rossjohn J, et al. (2012) Loss of Anti-Viral Immunity by Infection with a Virus Encoding a Cross-Reactive Pathogenic Epitope. PLoS Pathog 8(4): e1002633. doi:10.1371/journal.ppat.1002633. Link to article on publisher's site
Copyright: © 2012 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.