A SINGLE RESIDUE EXCHANGE WITHIN A VIRAL CTL EPITOPE ALTERS PROTEASOME-MEDIATED DEGRADATION RESULTING IN LACK OF ANTIGEN PRESENTATION

CTL epitope (KSPWFTTL) encoded by AKV/MCF type of murine leukemia viru s (MuLV) differs from the sequence in Friend/Moloney/Rauscher (FMR) ty pe in one residue (RSPWFTTL). CTL experiments indicated defective proc essing of the FMR peptide in tumor cells. Proteasome-mediated digestio n of AKV/MCF-type 26-mer peptides resulted in the early generation and higher levels of epitope-containing fragments than digestion of FWR-t ype peptides, explained by prominent cleavage next to R in the FMR seq uence. The fragments were identified as 10- and Il-mer peptides and we re efficiently translocated by TAP. The naturally presented AKV/MCF pe ptide is the 8-mer, indicating ER peptide trimming. In conclusion, a s ingle residue exchange can cause CTL epitope destruction by specific p roteasomal cleavage.