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


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??????? 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?????-specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses.

SUBMITTER: Chen AT 

PROVIDER: S-EPMC3334890 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Chen Alex T AT   Cornberg Markus M   Gras Stephanie S   Guillonneau Carole C   Rossjohn Jamie J   Trees Andrew A   Emonet Sebastien S   de la Torre Juan C JC   Welsh Raymond M RM   Selin Liisa K LK  

PLoS pathogens 20120419 4


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 sharin  ...[more]

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