title: 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 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.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Alex T
authors.initials: AT
authors.lastname: Chen
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Carole
authors.initials: C
authors.lastname: Guillonneau
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Andrew
authors.initials: A
authors.lastname: Trees
authors.forename: Sebastien
authors.initials: S
authors.lastname: Emonet
authors.forename: Juan C
authors.initials: JC
authors.lastname: de la Torre
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Welsh
authors.forename: Liisa K
authors.initials: LK
authors.lastname: Selin
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D008297:Male; D051379:Mice; D009154:Mutation; D018052:Pichinde virus / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins