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 wa s analysed using lymph node lymphocytes (LNL) from patients with color ectal carcinoma. LNL were stimulated with allogeneic, MUC1-transfected B cells and the bulk cultures were cloned, Alloreactive cytotoxic T c ell clones were obtained which preferentially lysed MUC1-expressing ta rgets. The majority was CD4(+) and MHC-class II-restricted, and a mino r group was CD8(+) and MHC-class I-restricted. All the clones expresse d CD3 and TCR alpha beta, and were CD56(-). The capacity to preferenti ally 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-li nked glycosylation in the targets. Furthermore, this effect was comple tely abrogated by the monoclonal antibody 3C9, directed against the Th omsen-Friedenreich antigen (T-antigen, Gal beta 1-3GalNAc bound alpha 1-3 to Ser/Thr) as well as by the soluble disaccharide Gal beta 1-3Gal NAc, but not by other similar disaccharides. The authors conclude that in their system the preferential killing of MUC1-expressing targets i s due to the recognition of an internal carbohydrate epitope accessibl e on underglycosylated MUC1, possibly T-antigen, by an auxiliary recep tor molecule on T cells.