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

Abstract

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.