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    Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope

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    Authors
    Chen, Alex T.
    Cornberg, Markus
    Gras, Stephanie
    Guillonneau, Carole
    Rossjohn, Jamie
    Trees, Andrew
    Emonet, Sebastien
    de la Torre, Juan C.
    Welsh, Raymond M.
    Selin, Liisa K.
    UMass Chan Affiliations
    Department of Pathology
    Document Type
    Journal Article
    Publication Date
    2012-04-19
    Keywords
    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
    Immunology and Infectious Disease
    Life Sciences
    Medicine and Health Sciences
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    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.
    Source
    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
    DOI
    10.1371/journal.ppat.1002633
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/39546
    PubMed ID
    22536152
    Related Resources
    Link to Article in PubMed
    Rights
    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.
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.ppat.1002633
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