Antigen presentation in Syrian hamster cells: substrate selectivity of TAPcontrolled by polymorphic residues in TAP1 and differential requirements for loading of H2 class I molecules

Expression of mouse major histocompatibility complex (MHC) class I molecule s in different cell lines derived from Syrian hamsters has revealed antigen presentation deficiencies of some H2 allelic products in two cell lines (B HK and NIL-2) which were overcome by transient expression of the rat transp orter associated with antigen processing (TAP; Lobigs et al. 1995). Here we show that in both cell lines the endogenous MHC class I cell surface expre ssion was completely down-regulated. Lymphokine treatment induced endogenou s and recombinant mouse MHC class I cell surface expression to levels simil ar to that in other Syrian hamster cell lines competent for antigen present ation through transduced H2 molecules. Accordingly, constitutive downregula tion of expression of accessory molecules of the MHC class I pathway can re veal differences between H2 class I alleles in antigen presentation not enc ountered when the expression levels are augmented. In addition to the diffe rential expression of MHC class I pathway genes, two cell lines representin g competent (FF) and defective (BHK) antigen presentation phenotypes for mo use class I MHC restriction elements demonstrated substantial sequence poly morphism in Tap1 but not Tap2. Cytokine-treated FF or BHK cells and human T AP-deficient T2 cells transfected with FF or BHK TAP1 in combination with F F TAP2 differed in their preference for C-terminal peptide residues, as sho wn by an in vitro peptide transport assay. Thus, polymorphic residues in TA P1 can influence the substrate selectivity of the Syrian hamster peptide tr ansporter.