Regulation of Qa-1 expression and determinant modification by an H-2D-linked gene, Qdm

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Abstract
We examined the regulation of cell surface expression of the Qa-1 alloantigens using a panel of monoclonal anti-Qa-1 cytotoxic T-lymphocyte (mCTL) lines. In contrast to previous reports of tissue-specific expression, we found that Qa-1 was widely expressed, resembling the prototypical class I H-2K/D molecules. We further found that an H-2D-linked gene, which we termed Qdm for Qa-1 determinant modifier, controlled expression of certain CTL-defined Qa-1 antigenic determinants. H-2D khomozygous haplotypes expressed a recessive allele of the modifier, Qdm k, whereas all other H-2 haplotypes tested expressed a dominant allele, Qdm +. The Qdm + allele regulated in trans Qa-1 epitope expression from a Qdm kchromosome, modifying expression of particular CTL-defined Qa-1 antigenic determinants rather than affecting levels of cell surface expression. Mechanisms of Qdm function may include either a novel protein modification system or an unprecedented case of antigen recognition restricted by a nonclassical major histocompatibility complex molecule.