Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope.
PLoS Pathog
; 8(4): e1002633, 2012.
Article
em En
| MEDLINE
| ID: mdl-22536152
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 NP205â212 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 NP38â45-specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
/
Receptores de Antígenos de Linfócitos T
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Vírus Pichinde
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Linfócitos T CD8-Positivos
/
Epitopos de Linfócito T
/
Coriomeningite Linfocítica
Limite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos