Carbohydrate Recognition on MUC1‐Expressing Targets Enhances Cytotoxicity of a T Cell Subpopulation

The influence of the epithelial mucin MUC1 on T cell‐mediated lysis was analysed using lymph node lymphocytes (LNL) from patients with colorectal carcinoma. LNL were stimulated with allogeneic, MUC1‐transfected B cells and the bulk cultures were cloned. Alloreactive cytotoxic T cell clones were obtained which preferentially lysed MUC1‐expressing targets. The majority was CD4+ and MHC‐class II‐restricted, and a minor group was CD8+ and MHC‐class I‐restricted. All the clones expressed CD3 and TCRαβ, and were CD56−. The capacity to preferentially kill MUC1‐expressing targets was stable in several clones for up to 6 months in culture. The enhancing effect of MUC1 on the lysis was investigated in more detail. It was only seen after inhibition of O‐linked glycosylation in the targets. Furthermore, this effect was completely abrogated by the monoclonal antibody 3C9, directed against the Thomsen–Friedenreich antigen (T‐antigen, Galβ1–3GalNAc bound α1–3 to Ser/Thr) as well as by the soluble disaccharide Galβ1–3GalNAc, but not by other similar disaccharides. The authors conclude that in their system the preferential killing of MUC1‐expressing targets is due to the recognition of an internal carbohydrate epitope accessible on underglycosylated MUC1, possibly T‐antigen, by an auxiliary receptor molecule on T cells.