MHC class I presentation of short peptides enables CD8+ T cell (TCD8+) immunosurveillance of tumors and intracellular pathogens. A key feature of the class I pathway is that the immunopeptidome is highly skewed from the cellular degradome, indicating high selectivity of the access of protease-generated peptides to class I molecules. Similarly, in professional antigen-presenting cells, peptides from minute amounts of proteins introduced into the cytosol outcompete an overwhelming supply of constitutively generated peptides. Here, we propose that antigen processing is based on substrate channeling and review recent studies from the antigen processing and cell biology fields that provide a starting point for testing this hypothesis.

Inserm 27 rue Juliette Dodu 750 10 Paris France; International Centre for Cancer Vaccine Science University of Gdańsk Science ul Wita Stwosza 63 80 308 Gdańsk Poland; Department of Medical Biosciences Umeå University 90187 Umeå Sweden; RECAMO Masaryk Memorial Cancer Institute Zluty kopec 7 65653 Brno Czech Republic

Laboratory of Viral Diseases National Institute of Allergy and Infectious Diseases Bethesda MD 20892 USA

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