Lack of evidence for MHC-unrestricted (atypical) recognition of mucin by mucinous pancreatic tumour-reactive T-cells

Cytotoxic T-cells generated against heterologous, mucinous pancreatic tumou r cells were shown to recognize mucin in a major histocombatibility complex (MHC)-unrestricted fashion. In contrast, the present study demonstrates a typical allogeneic response of heterologous cytotoxic T-cells established a gainst mucin-expressing pancreatic tumour cells. Heterologous cytotoxic T c ells lysed targets that were used as stimulators and other targets that sha red human leucocyte antigen (HLA) with the stimulator. These cytotoxic T-ce lls lysed mucin-expressing stimulator cells but not autologous tumour cells in spite of expressing mucin on their surface. Likewise, tumour-infiltrati ng CD4(+) T-cells proliferated against its own tumour cell target, while su ch T-cells did not respond to heterologous, mucin-expressing pancreatic tum our cells. Culturing heterologous tumour-specific cytotoxic T-cells with pu rified pancreatic tumour cell-mucin rendered them unresponsive to their tar get cells. Furthermore, purified mucin did not produce a mucin-specific res ponse in mucinous pancreatic tumour patients' primary T-cells even in the p resence of antigen-presenting cells. Our study finds no evidence for MHC-un restricted recognition of mucin by pancreatic cancer patients' T-cells. (C) 2000 Cancer Research Campaign.