Peptide transporter-independent, stress protein-mediated endosomal processing of endogenous protein antigens for major histocompatibility complex class I presentation.
The peptide transporter-defective cell line RMA-S expressing the wild-type simian virus 40 large T antigen (wtT-Ag) from a transfected gene did not present two well-defined, H-2 class I (Db)-restricted epitopes of T-Ag to cytotoxic T lymphocytes (CTL). Hence, "endogenous" processing and presentation of the wtT-Ag depended on a functional peptide transporter heterodimer. In contrast, both T-Ag epitopes were efficiently presented to CTL by transfected RMA-S cells expressing a truncated, cytoplasmic T-Ag variant (cT-Ag) or a karyophilic, amino-terminal 272-amino acid T-Ag fragment. Transporter-independent "endogenous" processing of mutant T-Ag molecules correlated with their association with the constitutively expressed heat shock protein 73 (hsp73). Class I-restricted presentation of both epitopes processed from these hsp73-associated protein antigens was sensitive to NH4Cl and chloroquine. These data indicate that selected intracellular proteins access an alternative, hsp73-mediated pathway for class I-restricted presentation that operates independent of peptide transporters in an endosomal compartment.
Institute for Microbiology, University of Ulm, FRG.
R
R
Schirmbeck
J
J
Reimann
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D006183:H-2 Antigens / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000952:Antigens, Polyomavirus Transforming; D002352:Carrier Proteins; D006183:H-2 Antigens; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; C489516:Tap2 protein, mouse