Multiple proteases process viral antigens for presentation by MHC class I molecules to CD8(+) T lymphocytes.
Recognition by CD8(+) cytotoxic T lymphocytes of any intracellular viral protein requires its initial cytosolic proteolytic processing, the translocation of processed peptides to the endoplasmic reticulum via the transporters associated with antigen processing, and their binding to nascent major histocompatibility complex (MHC) class I molecules that then present the antigenic peptides at the infected cell surface. From initial assumptions that the multicatalytic and ubiquitous proteasome is the only protease capable of fully generating peptide ligands for MHC class I molecules, the last few years have seen the identification of a number of alternative proteases that contribute to endogenous antigen processing. Trimming by non-proteasomal proteases of precursor peptides produced by proteasomes is now a well-established fact. In addition, proteases that can process antigens in a fully proteasome-independent fashion have also been identified. The final level of presentation of many viral epitopes is probably the result of interplay between different proteolytic activities. This expands the number of tissues and physiological and pathological situations compatible with antigen presentation, as well as the universe of pathogen-derived sequences available for recognition by CD8(+) T lymphocytes.
Centro Nacional de Microbiologi;a, Instituto de Salud Carlos III, Ctra. Pozuelo, Km 2, E-28220 Majadahonda, Madrid, Spain. mdval@isciii.es
Margarita
M
Del-Val
Daniel
D
López
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D000956:Antigens, Viral / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000502:physiology; D010450:Endopeptidases / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D011948:Receptors, Antigen, T-Cell; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex