Cytokines increase transporter in antigen processing-1 expression more rapidly than HLA class I expression in endothelial cells.
Transporter in Ag processing-1 (TAP-1, previously called PSF-1 or Ring-4) is an MHC-encoded gene product that is required for efficient association of intracellular peptide Ag with nascent HLA class I H chain and beta 2-microglobulin, thereby permitting assembly and normal surface expression of the class I molecules. TAP-1 is thought to function as a component of a transmembrane pump, that transports cytoplasmically-derived peptides into the lumen of the endoplasmic reticulum where class I molecules assemble. Synthesis and expression of HLA class I molecules is increased in human endothelial cells by IFN-beta, IFN-gamma, and TNF. We report these same cytokines increase TAP-1 expression. As with class I, TAP-1 is also synergistically increased by combinations of TNF with IFN. Interestingly, cytokine-induced increases in TAP-1 mRNA are markedly more rapid than increases in class I mRNA. This rapid increase in TAP-1 mRNA is reflected in a rapid increase in TAP-1 protein. These results demonstrate that TAP-1 synthesis and class I synthesis are regulated in parallel. The rapidity of the cytokine response of TAP-1 compared to class I further suggests that the constitutive level of TAP-1 expression in endothelial cells is not sufficient to support inducible increases in class I expression.
Epperson
D E
DE
Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510.
Arnold
D
D
Spies
T
T
Cresswell
P
P
Pober
J S
JS
Johnson
D R
DR
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons