The HA-2 minor histocompatibility antigen is derived from a diallelic geneencoding a novel human class I myosin protein

Human minor histocompatibility Ags (mHag) present significant barriers to s uccessful bone marrow transplantation. However, the structure of human mHag and the basis for antigenic disparities are still largely unknown. Here we report the identification of the gene encoding the human mHag HA-2 as a pr eviously unknown member of the class I myosin family, which we have designa ted MYO1G. The gene is located on the short arm of chromosome 7. Expression of this gene is limited to cells of hemopoietic origin, in keeping with th e previously defined tissue expression of the HA-2 Ag. RT-PCR amplification of MYO1G from different individuals led to the identification of two genet ic variants, designated MYO1G(V) and MYO1G(M). The former encodes the pepti de sequence previously shown to be the HA-2 epitope (YIGEVLVSV), whereas th e latter shows a single amino acid change in this peptide (YIGEVLVS (M) und er bar). This change has only a modest effect on peptide binding to the cla ss I MHC-restricted element HLA-A*0201, and a minimal impact on recognition by T cells when added exogenously to target cells. Nonetheless, as detecte d using either T cells or mass spectrometry, this amino acid change results in a failure of the latter peptide to be presented at the surface of cells that express MYO1G(M) endogenously. These studies have thus identified a n ew mHag-encoding gene, and thereby provide additional information about bot h the genetic origins of human mHag as well as the underlying basis of an A g-positive vs Ag-negative state.