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 tumour 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 against mucin-expressing pancreatic tumour cells. Heterologous cytotoxic T cells lysed targets that were used as stimulators and other targets that shared human leucocyte antigen (HLA) with the stimulator. These cytotoxic T-cells lysed mucin-expressing stimulator cells but not autologous tumour cells in spite of expressing mucin on their surface. Likewise, tumour-infiltrating CD4+ T-cells proliferated against its own tumour cell target, while such T-cells did not respond to heterologous, mucin-expressing pancreatic tumour cells. Culturing heterologous tumour-specific cytotoxic T-cells with purified pancreatic tumour cell-mucin rendered them unresponsive to their target cells. Furthermore, purified mucin did not produce a mucin-specific response in mucinous pancreatic tumour patients' primary T-cells even in the presence of antigen-presenting cells. Our study finds no evidence for MHC-unrestricted recognition of mucin by pancreatic cancer patients' T-cells.
Selvan
R S
RS
Department of Surgery, Duke University, Medical Center, Durham, NC 27710, USA.
Pappas
T N
TN
Ward
F E
FE
D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008285:Major Histocompatibility Complex; D009077:Mucins / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D009077:Mucins