Virus infection blocks the processing and presentation of exogenous antigen with the major histocompatibility complex class II molecules.
Helper T cell recognition of antigen requires that antigen be processed and presented by class II expressing antigen-presenting cells (APC). Many antigens presented by the immune system are part of infectious organisms, for example, bacteria and viruses, which themselves may affect APC function. Here we show that infection of B cell lines as APC with viruses of two different families, namely, influenza A or vaccinia, completely block processing and presentation of an exogenous globular protein antigen pigeon cytochrome c. The block appears to be primarily within the processing pathway, as virus infection has little effect on the presentation of an antigenic peptide of pigeon cytochrome c which does not require processing. It is likely that several steps in the processing pathway are affected. Only live infectious virus, not UV-inactivated virus blocks APC function, indicating that there is no competition of viral particles with cytochrome c for the class II processing machinery. As compared to uninfected cells, virus-infected cells internalize less antigen bound to surface Ig but degrade a similar portion of that which enters the cell. Virus infection results in reduced protein synthesis in APC which may also be a factor in decreasing APC function. Significantly, we show that the processing of a high affinity evolutionary variant of cytochrome c from Drosophila melanogaster is reduced less by virus infection as compared to c. Such knowledge may guide the selection of antigenic epitopes in vaccine design.
Domanico
S Z
SZ
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500.
Pierce
S K
SK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002460:Cell Line; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D014176:Protein Biosynthesis; D012555:Schistosomiasis mansoni / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D014765:Viral Vaccines