Constitutive and inducible expression of the epithelial antigen MUC1 (CD227) in human T cells.
MUC1 (CD227) is a large glycoprotein normally produced by epithelial tissue and expressed aberrantly in carcinomas. Here we show that resting human T cells express basal levels of MUC1 mRNA and protein forms with molecular masses of approximately 150 and approximately 250 intracellularly, but lack surface expression. Mitogenic stimulation induces the appearance of new MUC1 mRNA and >300-kDa MUC1 forms. Concomitantly, MUC1 is translocated to the outer cell membrane and its density is continuously modulated according to the cycling status. Inhibitors of mRNA and protein synthesis and of Golgi-dependent protein transport prevent MUC1 induction. Ligation of surface MUC1 has no effect on T-cell proliferation. Also, altering the overall protein structure by preventing glycosylation has no effect. Sizable amounts of >300-kDa glycosylated MUC1 forms are shed by proliferating T cells. This soluble MUC1 does not appear to influence T-cell response, and we found no evidence for MUC1 binding sites on T cells or for transfer of the protein on cell-cell contact. We therefore suggest that MUC1 fulfills the criteria for an early T-cell activation marker but its function remains to be determined. Finally, although we found that cancer- and T cell-associated MUC1 expose common protein core and sialylated epitopes, there is a peptide region, accessible in carcinomas due to an aberrant glycosylation, that is stably not accessible in T cells with potential implications for cancer immunotherapy.
Fattorossi
Andrea
A
Ist. di Ostetricia e Ginecologia, Univ. Cattolica del Sacro Cuore, Rome, Italy. cytogyn@rm.unicatt.it
Battaglia
Alessandra
A
Malinconico
Paolo
P
Stoler
Andrea
A
Andreocci
Leila
L
Parente
Dino
D
Coscarella
Annamaria
A
Maggiano
Nicola
N
Perillo
Alessandro
A
Pierelli
Luca
L
Scambia
Giovanni
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000494:pharmacology; D018275:Carcinoma, Lobular / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008970:Molecular Weight; D018396:Mucin-1 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D000941:Antigens; D017252:CD3 Complex; D018396:Mucin-1; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D003609:Dactinomycin; D013755:Tetradecanoylphorbol Acetate