Form and pattern of MUC1 expression on T cells activated in vivo or in vitro suggests a function in T-cell migration.
MUC1 is a transmembrane mucin that is expressed on ductal epithelial cells and epithelial malignancies and has been proposed as a target antigen for immunotherapy. The expression of MUC1 has recently been reported on T and B cells. In this study we demonstrate that following activation in vivo or activation by different stimuli in vitro, human T cells expressed MUC1 at the cell surface. However, the level of expression in activated human T cells was significantly lower than that seen on normal epithelial cells or on breast cancer cells. In contrast, resting T cells did not bind MUC1-specific monoclonal antibodies (mAbs), nor was MUC1 mRNA detectable by reverse transcription-polymerase chain reaction (RT-PCR) or Northern blot analysis in these cells. The profile of activated T-cell reactivity with different MUC1-specific antibodies suggested that the glycoform of MUC1 expressed by the activated T cells carried core 2-based O-glycans, as opposed to the core 1 structures that dominate in the cancer-associated mucin. Confocal microscopy revealed that MUC1 was uniformly distributed on the surface of activated T cells. However, when the cells were polarized in response to a migratory chemokine, MUC1 was found on the leading edge rather than on the uropod, where other large mucin-like molecules on T cells are trafficked. The concentration of MUC1 at the leading edge of polarized activated human T cells suggests that MUC1 could be involved in early interactions between T cells and endothelial cells at inflammatory sites.
Correa
Isabel
I
Cancer Research UK, Breast Cancer Biology Group, Guy's Hospital, London, UK.
Plunkett
Tim
T
Vlad
Anda
A
Mungul
Arron
A
Candelora-Kettel
Jessica
J
Burchell
Joy M
JM
Taylor-Papadimitriou
Joyce
J
Finn
Olivera J
OJ
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured / Q000276:immunology; D005260:Female; D015870:Gene Expression; D016695:Glycosyltransferases / Q000096:biosynthesis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments; D012333:RNA, Messenger; D016695:Glycosyltransferases