Tobacco reduces membrane HLA class I that is restored by transfection with transporter associated with antigen processing 1 cDNA.
HLA class I molecules are recognized by CTL that eliminate virally infected and malignantly transformed cells presenting foreign peptide-a process termed immunosurveillance. Many tumors have reduced levels of membrane HLA class I. Tumor cells with mutations that reduce HLA class I avoid immunosurveillance and continue to proliferate. As tobacco use can induce tumors, we examined the effect of tobacco extracts on membrane HLA class I. These studies show that culture of cells in media containing tobacco extracts reduces membrane HLA class I, but not other proteins, on primary keratinocytes and other cell types. Culture in tobacco extracts, but not extracts of other substances, reduces TAP1 protein, but does not reduce expression of HLA class I H chain, L chain, or the housekeeping protein beta-actin. The reduction of TAP1 protein occurs within 4 h and is dose-dependent. Culture in tobacco extracts reduces TAP1 protein abundance, but not steady-state mRNA abundance. Tobacco-treated cells show defects in HLA class I biosynthesis similar to those found in TAP1-deficient cell lines. Transfection with TAP1 cDNA restores TAP1 protein abundance, HLA class I biosynthesis, and cell surface expression. Combined, these data show that culture in tobacco extracts reduces TAP1 protein abundance and membrane HLA class I levels. Reduction in membrane HLA class I could permit subsequent malignant transformation of cells to be undetected by the immune system.
Fine
Craig I
CI
Department of Biological Sciences, College of Dentistry, New York University, New York, NY 10010, USA.
Han
C David
CD
Sun
Xuming
X
Liu
Yuexun
Y
McCutcheon
Jane A
JA
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003470:Culture Media; D018076:DNA, Complementary / Q000235:genetics*; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010936:Plant Extracts / Q000633:toxicity; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014026:Nicotiana / Q000633:toxicity*; D014162:Transfection
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D003470:Culture Media; D018076:DNA, Complementary; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D010936:Plant Extracts; D012333:RNA, Messenger; C073119:TAP1 protein, human