MHC CLASS-I PRESENTATION OF AN EXOGENOUS POLYPEPTIDE ANTIGEN ENCODED BY THE MURINE AIDS DEFECTIVE VIRUS

Peptides derived from endogenous proteins are presented by MHC class I molecules, whereas those derived from exogenous proteins are presente d by MHC class II molecules. This strict segregation has been reconsid ered in recent reports in which exogenous antigens are shown to be pre sented by MHC class I molecules in the phagocytic pathway. In this rep ort, the presentation pathway of an exogenously added highly antigenic polypeptide encoded by the murine AIDS (MAIDS) defective virus gag p1 2 gene is investigated. A 25-mer polypeptide (P12-25) encoded within t he gag p12 region of the MAIDS defective virus was found to be effecti ve in stimulating unprimed B6 (H-2(b)) CD8(+) T cells in vitro. The pr esentation of P12-25 is sensitive to cytochalasin B and D, brefeldin A and gelonin, a ribosome-inactivating protein synthesis inhibitor, but less sensitive or resistant to lactacystin, a highly specific inhibit or of the proteasome. Interestingly, CA-074, a selective inhibitor of cathepsin B, inhibited presentation of the polypeptide, indicating its involvement in the degradation of the P12-25 polypeptide. In fact, wh en P12-25 was digested with purified cathepsin B in vitro, a highly an tigenic Il-mer peptide containing the class I (H-2D(b))-binding motif was obtained. Our results favor the phagosome/macropinosome-to-cytosol -to-endoplasmic reticulum (ER)-to-cell surface pathway for exogenous a ntigens presented by MHC class I molecules. These findings may be rele vant to exploiting peptide vaccines that specifically elicit CD8(+) T cell immunity in vivo.