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PLoS Pathog. 2012;8(4):e1002633. doi: 10.1371/journal.ppat.1002633. Epub 2012 Apr 19.

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

Author information

1
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

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.

PMID:
22536152
PMCID:
PMC3334890
DOI:
10.1371/journal.ppat.1002633
[Indexed for MEDLINE]
Free PMC Article

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