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Hypothesis: MHC class I, rather than just a flagpole for CD8+ T cells is also a protease in its own right
1Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Ever since the discovery of MHC class I restriction and the onslaught of the dual receptor hypothesis, MHC class I has been perceived as a passive entity in TCR recognition and the appropriate antigen processing and presentation pathways. However, numerous experimental observations and theoretical considerations are difficult or unable to be explained by the accepted mechanism of class I antigen presentation. Proteases within and outside the endoplasmic reticulum (ER) are evoked to be solely responsible for the generation of the appropriate 8-10 amino acid-long peptides associated with MHC class I. A MHC class I with site-restricted ER protease activity would overcome most of the present difficulties in explaining MHC class I antigen presentation.
Ever since the discovery of MHC class I restriction and the onslaught of the dual receptor hypothesis, MHC class I has been perceived as a passive entity in TCR recognition and the appropriate antigen processing and presentation pathways. However, numerous experimental observations and theoretical considerations are difficult or unable to be explained by the accepted mechanism of class I antigen presentation. Proteases within and outside the endoplasmic reticulum (ER) are evoked to be solely responsible for the generation of the appropriate 8-10 amino acid-long peptides associated with MHC class I. A MHC class I with site-restricted ER protease activity would overcome most of the present difficulties in explaining MHC class I antigen presentation.