Form and pattern of MUC1 expression on T cells activated in vivo or in vitro suggests a function in T‐cell migration

Abstract

SUMMARYMUC1 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.

Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1

“…Although MUC1 is expressed by gastrointestinal epithelial cells, pancreas, respiratory tract 1,2 and even activated lymphocytes, 41 the mucin is not apparently expressed in the thymus. 2 Thus, any elimination of reactive T cells is likely to occur through cross-priming by DCs.…”

MUC1 Oncoprotein Regulates Bcr-Abl Stability and Pathogenesis in Chronic Myelogenous Leukemia Cells

“…The MUC1 transmembrane glycoprotein is expressed by normal secretory epithelial cells (10) and hematopoietic cells of the lymphoid lineage (11,12). Diverse human carcinomas aberrantly overexpress MUC1 (10).…”

Recombinant MUC1 mucin with a breast cancer-like O-glycosylation produced in large amounts in Chinese-hamster ovary cells

“…MUC1 was first identified as an epithelial cell protein [1], but has recently also been found at low levels on cells of haematopoietic origin [2][3][4]. The expression of MUC1 is elevated in many forms of epithelial cancers, including those of the breast, lung, cervix, colon and pancreas [5,6].…”