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 (D-b)-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.