Antigens and autophagy: the path less travelled?
The Epstein-Barr virus (EBV)-coded nuclear antigen (EBNA) 1, a latent cycle protein endogenously expressed in EBV-transformed B lymphoblastoid cell lines (LCLs), is reported to be processed for CD4(+) T cell recognition by an intracellular route involving antigen delivery to the endosome/lyosome (MHC class II loading) compartment via macroautophagy. In contrast we find that, in the same cell type, two other virus-coded nuclear proteins of the latent cycle, EBNA2 and EBNA3C, are processed by a different route that is unaffected by autophagy inhibition. This involves the intercellular transfer of an antigenic moiety, detectable in cell-free culture supernatants, and its uptake and processing as exogenous antigen by neighboring cells. The process is cumulative and leads over several days of LCL culture to high levels of CD4+ T cell epitope display. The presentation of certain EBV lytic cycle proteins to CD4+ T cells has also recently been found to involve a similar intercellular antigen transfer. It becomes important to know why, even in the same cell type, some antigens but not others appear to access the MHC class II presentation pathway by autophagy.
Taylor
Graham S
GS
Cancer Research UK, Institute for Cancer Studies, University of Birmingham, Vincetn Drive, Birmingham, United Kingdom. G.S.Taylor@bham.ac.uk
Rickinson
Alan B
AB
D017951:Antigen Presentation / Q000502:physiology*; D000941:Antigens / Q000502:physiology*; D000956:Antigens, Viral / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005802:Genes, MHC Class II / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D014764:Viral Proteins / Q000276:immunology
D000941:Antigens; D000956:Antigens, Viral; C402641:EBNA-2 protein, Human herpesvirus 4; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1