Short peptides sensitize target cells to CTL specific for the MHC class Ib molecule, H2-M3

The MHC class Ib molecule H2-M3 presents N-formylated peptides from the N terminus of proteins encoded by the mitochondrial genome to CTL. A panel of CTL specific for a peptide derived from a mitochondrial protein, either COI or ND1, was used to determine the optimal peptide length for sensitizing antigen-deficient target cells. All long-term CTL lines and most CTL clones lysed target cells sensitized with either a COI hexamer or an ND1 heptamer. Only 3 out of 12 anti-ND1 clones preferred an octamer or nonamer peptide and no CTL required to longer peptides. The CTL preference for short peptides matches a shortened groove in M3. The CTL all lysed lymphoblasts encoding the appropriate mitochondrial antigen, suggesting that these target cells express naturally processed, endogenous, formylated peptides, ranging from six to nine amino acids in length.