Jr. Rodgers et al., SURFACE EXPRESSION OF BETA(2)-MICROGLOBULIN-ASSOCIATED THYMUS-LEUKEMIA ANTIGEN IS INDEPENDENT OF TAP2, European Journal of Immunology, 25(4), 1995, pp. 1001-1007
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.