SEQUENCE, LINKAGE TO H2-K, AND FUNCTION OF MOUSE TAPASIN IN MHC CLASS-I ASSEMBLY

Assembly of major histocompatibility complex (MHC) class I molecules i n human cells is dependent on the accessory protein tapasin, which med iates their interaction with the transporters associated with antigen processing (TAP) and thereby ensures efficient peptide binding. Analys is of a mouse tapasin complementary DNA defined a conserved polypeptid e sharing sequences diagnostic of a transmembrane protein related to t he immunoglobulin superfamily, and an endoplasmic reticulum retention motif. The mouse tapasin gene was mapped about 70 kilobases from H2-K at the centromeric end of the mouse MHC. Expression of mouse tapasin i n a tapasin-deficient human mutant cell line restored the normal assem bly and expression of class I alleles. Thus? tapasin is a structurally and functionally conserved component of the MHC class I antigen proce ssing pathway. Its genetic linkage to the class I and TAP subunit gene s in the MHC map be of significance in the coordinate expression and f unctional coadaptation of the diverse gene products.