Alternative pathways for processing exogenous and endogenous antigens thatcan generate peptides for MHC class I-restricted presentation

The concept of distinct endogenous and exogenous pathways for generating pe ptides for MHC-I and MHC-II-restricted presentation to CD4(+) or CD8(+) T c ells fits well with the bulk of experimental data. Nevertheless, evidence i s emerging for alternative processing pathways that generate peptides for M HC-I-restricted presentation. Using a well characterized, particulate viral antigen of prominent medical importance (the hepatitis B surface antigen), we summarize our evidence that the efficient, endolysosomal processing of exogenous antigens can lead to peptide-loaded MHC-I molecules. In addition, we describe evidence for endolysosomal processing of mutant, stress protei n-bound, endogenous antigens that liberate peptides binding to (and present ed by) MHC-I molecules. The putative biological role of alternative process ing of antigens generating cytotoxic T-lymphocyte-stimulating epitopes is d iscussed.