Epitopes described in "Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes."

Article Authors:P Klenerman; R M Zinkernagel
Article Title:Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes.
Reference Detail
Reference ID:1000793
Abstract:Some viruses, including human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in humans, and lymphocytic choriomeningitis virus (LCMV) in mice, are initially controlled by cytotoxic T lymphocytes (CTLs), but may subsequently escape through mutation of the relevant T-cell epitope. Some of these mutations preserve the normal binding to major histocompatibility complex class I molecules, but present an altered surface to the T-cell antigen receptor. The exact role of these so-called altered peptide ligands in vivo is not clear. Here we report that mice primed with LCMV-WE strain respond to a subsequent infection by WE-derived CTL epitope variants with a CTL response directed against the initial epitope rather than against the new variant epitope. This phenomenon of 'original antigenic sin' was initially described in influenza and is an asymmetric pattern of protective antibody crossreactivity determined by exposure to previously existing strains, which may therefore extend to some CTL responses. Original antigenic sin by CTL leads to impaired clearance of variant viruses infecting the same individual and so may enhance the immune escape of mutant viruses evolving in an individual host.
Affiliations:Institute for Experimental Immunology, University Hospital, Zurich, Switzerland.
Reference Type:Literature
PubMed ID:9697771
Journal Volume:394
Article Pages:482-5
Journal ISSN:1476-4687
Article Chemical List:Epitopes, T-Lymphocyte
Article MeSH List:Animals; Epitopes, T-Lymphocyte(genetics; immunology); Lymphocytic Choriomeningitis(immunology); Lymphocytic choriomeningitis virus(genetics; immunology); Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Models, Immunological; Mutation; T-Lymphocytes, Cytotoxic(immunology)
Curation Last Updated:2016-01-08 20:12:19