Surface expression of beta 2-microglobulin-associated thymus-leukemia antigen is independent of TAP2.
Mouse thymus-leukemia antigen (TL), like other major histocompatibility complex (MHC) class I-b antigens, displays signs of a specialized function. 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 this narrow range of tissue distribution. Like most other class I molecules, TL is dependent upon endogenous beta 2-microglobulin (beta 2m) for transport to the surface. However, here we show that unlike most other MHC class I molecules, TL is expressed efficiently in the absence of functional transporter associated with antigen processing subunit 2 (TAP2). A putative fourth TLa gene cloned from A.SL1 cells was expressed in RMA and RMA-S cells. In bulk transformants, TL expression is higher in TAP2-RMA-S cells than in wild-type RMA cells, and is not elevated by incubation at reduced temperatures or exposure to exogenous beta 2m. Analysis of immunoprecipitated molecules by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicates that TL is processed normally in RMA-S cells and is associated with beta 2m 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-dependent peptides, this class I-b molecule does not require them for efficient export to, and stable expression at the cell surface.
Rodgers
J R
JR
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Mehta
V
V
Cook
R G
RG
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D001692:Biological Transport; D018076:DNA, Complementary; D018014:Gene Transfer Techniques; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology*; D013945:Thymoma / Q000276:immunology; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000378:metabolism* / Q000494:pharmacology
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; C489516:Tap2 protein, mouse; D001613:beta 2-Microglobulin; C028388:thymus-leukemia antigens