Maternally transmitted histocompatibility antigen of mice: A hydrophobic peptide of a mitochondrially encoded protein

MTF, a murine minor histocompatibility antigen, is maternally inherited and thought to be encoded by a mitochondrial gene. We sequenced the entire mitochondrial genomes from three strains that differ in MTF Mtf^β, Mtf^γ, and Mtf^δ) and compared the sequences with the known, Mtf^α, mitochondrial DNA sequence. We found only one site where all four genomes differed, affecting amino acid residue 6 of ND1, a subunit of NADH dehydrogenase. Incubation of non-Mtf^α target cells with synthetic peptide ND1α1-17 (the first 17 amino acids of the ND1 protein of Mtf^α mice) rendered them susceptible to lysis by MTF^α-specific cytotoxic T cells (CTLs). Similarly, non-Mtf^β target cells were lysed by MTF^β-specific CTLs after incubation with the allelic form ND1β1-17. Thus, Mtf is attributable to allelic variation at a single residue of the ND1 protein. Cells can therefore display peptides derived from mitochondrially encoded proteins, and such peptides can be histocompatibility antigens.