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

Immunol Rev. 1999 Dec;172:131-52. doi: 10.1111/j.1600-065x.1999.tb01362.x.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Carrier Proteins / metabolism
  • Endocytosis
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins*
  • Hepatitis B Surface Antigens / administration & dosage
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B Vaccines / administration & dosage
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Mice
  • Peptides / immunology*
  • Peptides / metabolism*
  • Phagocytosis


  • Antigens
  • Carrier Proteins
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Histocompatibility Antigens Class I
  • Hspa8 protein, mouse
  • Peptides