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. / Experimental Surgery
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/458 |
| Date | 11 1900 |
| Creators | Konowalchuk, Jeffrey |
| Contributors | Agrawal, Babita (Surgery), Anderson, Colin (Surgery), Rayat, Gina (Surgery), Suresh, Mavanur (Pharmacy) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Format | 1072395 bytes, application/pdf |
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