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Permanent link (DOI): https://doi.org/10.7939/R39P9Z
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MUC1 is a novel costimulatory and coinhibitory molecule of human T cells Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
- Supervisor and department
Agrawal, Babita (Surgery)
- Examining committee member and department
Anderson, Colin (Surgery)
Rayat, Gina (Surgery)
Suresh, Mavanur (Pharmacy)
Department of Surgery
- Date accepted
- Graduation date
Master of Science
- Degree level
MUC1, a protein of epithelial and carcinoma cells, has recently been shown on activated T cells where it inhibits CD3-stimulated proliferation. Two immunoregulatory domains similar to ITAM and ITIMs are present on its cytoplasmic tail, suggesting that MUC1 can act as both a costimulatory and coinhibitory molecule of T cells. In my work, I have examined immunoregulatory function of MUC1 on human T cells.
We first showed that MUC1, when ligated in a population of unpurified T cells with an anti-CD3 and a crosslinking antibody, enhances proliferative and cytokine responses in a NF-AT-dependent manner by recruiting the AP-1 transcription factor and translocating it into the nucleus. With purified CD3+ T cells, we instead observed inhibition after MUC1/CD3 coligation and crosslinking. Reconstituting with irradiated CD3- cells, we discovered that MUC1 costimulation is dependent on the amount of accessory cells.
These data imply a novel role for MUC1 in T cell immunoregulation.
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