Loss of Anti-Viral Immunity by Infection with a Virus Encoding a Cross-Reactive Pathogenic Epitope

PLoS Pathogens

Stephanie Gras¹  Jamie Rossjohn¹  Juan C. de la Torre²  Andrew Trees²  Sebastien Emonet²  Carole Guillonneau³  Raymond M. Welsh⁴  Alex T. Chen⁴  Liisa K. Selin⁴  Markus Cornberg⁴ 

[1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia;Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America;Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia;Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America

关键词: T cells;    Immune response;    Cytotoxic T cells;    Fats;    Cell-mediated immunity;    Cloning;    Viral pathogens;    Hepatitis C virus;   

DOI  :  10.1371/journal.ppat.1002633

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY