Cell surface expression of major histocompatibility class I antigens is modulated by P-glycoprotein transporter.
P-glycoprotein (Mdr1), a member of the ABC superfamily, is a pump able to transport several compounds across plasma membranes. It displays a high level of similarity with the MHC-linked transporters TAP1 and TAP2 which are involved in the delivery of immunogenic peptides across the endoplasmic reticulum. In the present study we analyze the P-glycoprotein's ability to interfere with the biosynthetic pathway of the MHC class I molecules. Our results show that P-glycoprotein is involved in the modulation of the MHC class I expression in multidrug-resistant tumor cell lines, COS1 cells transfected with mdr1 gene, and human T lymphocytes. Epitope screening evokes the possibility that P-glycoprotein induces a modulation of the different MHC class I forms expressed on the cell surface. We propose that P-glycoprotein is involved in the transport of antigenic protein fragments from the cytosol into the endoplasmic reticulum. The suggested mechanism could be physiologically relevant in tissues displaying a high Mdr1 activity, where this transporter could contribute to the regulation of locoregional immune responses.
Masci
A M
AM
Department of Experimental Medicine, University of Rome La Sapienza, Italy.
Scala
S
S
Racioppi
L
L
Zappacosta
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern / Q000379:methods; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics; D006680:HLA Antigens / Q000096:biosynthesis* / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D014162:Transfection; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D014700:Verapamil