Department of Pathology
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
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.
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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.
DOI of Published Version
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
Chen, Alex T.; Cornberg, Markus; Gras, Stephanie; Guillonneau, Carole; Rossjohn, Jamie; Trees, Andrew; Emonet, Sebastien; de la Torre, Juan C.; Welsh, Raymond M.; and Selin, Liisa K., "Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope" (2012). Open Access Articles. 2340.