MUC1 is a novel costimulatory and coinhibitory molecule of human T cells

• Author / Creator

  Konowalchuk, Jeffrey

• 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.

• Subjects / Keywords

  • NF-AT
  • T cell
  • Coinhibition
  • MUC1
  • Costimulation

• Graduation date

  Fall 2009

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R39P9Z

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.