SURFACE EXPRESSION OF BETA(2)-MICROGLOBULIN-ASSOCIATED THYMUS-LEUKEMIA ANTIGEN IS INDEPENDENT OF TAP2

Mouse thymus-leukemia antigen (TL), like other major histocompatibilit y complex (MHC) class I-b antigens, displays signs of a specialized fu nction. It is normally expressed at high levels on immature thymocytes and at moderate levels on gut epithelium and activated mature T cells . A promoter/enhancer region unique among class I genes accounts for t his narrow range of tissue distribution. Like most other class I molec ules, TL is dependent upon endogenous beta(2)-microglobulin (beta(2)m) for transport to the surface. However, here we show that unlike most other MHC class I molecules, TL is expressed efficiently in the absenc e of functional transporter associated with antigen processing subunit 2 (TAP2). A putative fourth TL(a) gene cloned from A.SL1 cells was ex pressed in RMA and RMA-S cells. In bulk transformants, TL expression i s higher in TAP2(-) RMA-S cells than in wild-type RMA cells, and is no t elevated by incubation at reduced temperatures or exposure to exogen ous beta(2)m. Analysis of immunoprecipitasted molecules by polyacrylam ide gel electrophoresis in the presence of sodium dodecyl sulfate indi cates that TL is processed normally in RMA-S cells and is associated w ith beta(2)m both intracellularly and at the cell surface. However, TL heavy chains expressed on the cell surface in the absence of TAP2 are cleaved to a predominant 38 kDa fragment, presumably the result of an altered conformation that renders TL more susceptible to proteolysis. These results suggest that while TL may normally acquire TAP2-depende nt peptides, this class I-b molecule does not require them for efficie nt export to, and stable expression at the cell surface.