PATR-A AND PATR-B, THE ORTHOLOGUES OF HLA-A AND HLA-B, PRESENT HEPATITIS-C VIRUS EPITOPES TO CD8(-CELLS FROM 2 CHRONICALLY INFECTED CHIMPANZEES() CYTOTOXIC T)

Common chimpanzees (Pan troglodytes) infected with hepatitis C virus ( HCV) show a disease progression similar to that observed for human pat ients, Although most infected animals develop a chronic hepatitis, vir us persistence is associated with an ongoing immune response, for whic h the beneficial or detrimental effects are uncertain. Lines of virus- specific cytotoxic CD8(+) T lymphocytes (CTL) have been previously est ablished from liver biopsies of two common chimpanzees chronically inf ected with HCV-1. The viral epitopes recognized by six lines of CTL ha ve been defined using synthetic peptides and shown to consist of 8 to 9-residue peptides derived from various viral proteins. Five of the ep itopes derive from sequences that vary among strains of HCV, The major ity of the corresponding variant epitopes from different HCV strains w ere either recognized less efficiently or not at all by the CTL, sugge sting their response may have limited potential for controlling replic ation of HCV variants, Complementary DNAs encoding the class I alleles of che two common chimpanzees, Parr-A, -B, and -C were cloned, sequen ced, and transfected individually into a class I-deficient human cell line. Analysis of peptide presentation by the class I transfectants re , CTL identified the Patr class I allotypes that present the six epito pes defined here and an additional epitope defined previously. The ass ignment of epitopes to class I allotypes based upon analysis of the tr ansfected cells correlates precisely with the segregation of antigen-p resenting function within a panel of common chimpanzee cell lines and the expression of class I heavy chains as defined by isoelectric focus ing. Five of the HCV-1 epitopes are presented by Patr-B allotypes, two epitopes are presented by a Patr-A allotype, and none is presented by Patr-C allotypes.