Alternative pathways for processing exogenous and endogenous antigens that can generate peptides for MHC class I-restricted presentation.
The concept of distinct endogenous and exogenous pathways for generating peptides for MHC-I and MHC-II-restricted presentation to CD4+ or CD8+ T cells fits well with the bulk of experimental data. Nevertheless, evidence is emerging for alternative processing pathways that generate peptides for MHC-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 protein-bound, endogenous antigens that liberate peptides binding to (and presented by) MHC-I molecules. The putative biological role of alternative processing of antigens generating cytotoxic T-lymphocyte-stimulating epitopes is discussed.
Reimann
J
J
Department of Medical Microbiology and Immunology, University of Ulm, Germany. joerg.reimann@medizin.uni-ulm.de
Schirmbeck
R
R
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D004705:Endocytosis; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis
D000941:Antigens; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D015395:Histocompatibility Antigens Class I; C494372:Hspa8 protein, mouse; D010455:Peptides