IDENTIFICATION OF THE RAT MATERNALLY TRANSMITTED MINOR HISTOCOMPATIBILITY ANTIGEN

The rat maternally transmitted Ag has been previously described as a m inor histocompatibility Ag composed of a mitochondrially transmitted f actor (MTF) and the RT1.A(a) MHC class I molecule. We compared the DNA sequences of the 13 mitochondrial open reading frames from different rat strains and identified four coding polymorphisms that correlated w ith this MTF. We used synthetic 17-mer peptides spanning the polymorph isms to sensitize appropriate target cells in lymphocytotoxicity assay s and found that the MTF is derived from an internal region of ATPase 6. A tridecameric derivative of the ATPase 6 17 mer (termed 13N3E) cou ld sensitize RT1.A(a)-expressing target cells at picomolar concentrati ons and, when present on such cells, could compete fully with the natu ral ligand in cold-target competition assays, Comparing the 13N3E pept ide with the known peptide-binding requirements of RT1.A(a) suggested two possible binding conformations, placing either an internal or a C- terminal arginine in the F pocket of the peptide-binding groove. Argum ents favoring a ''bulging'' conformation, with N- and C-terminal resid ues bound into their conserved pockets, are discussed.