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 Mtfβ, Mtfγ, and Mtfδ) and compared the sequences with the known, Mtfα, 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-Mtfα target cells with synthetic peptide ND1α1-17 (the first 17 amino acids of the ND1 protein of Mtfα mice) rendered them susceptible to lysis by MTFα-specific cytotoxic T cells (CTLs). Similarly, non-Mtfβ target cells were lysed by MTFβ-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. © 1990.