1. Cytotoxic T lymphocytes from humans with adenocarcinomas stimulated by native MUC1 mucin and a mucin peptide mutated at a glycosylation site
- Author
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Nichol Dolby, Ji Yuan Wu, Ramila Philip, Karen E. Lowe, Lydia Kilinski, Stephen E. Wright, Sohel Talib, Jane S. Lebkowski, Janet S. Burnside, and Kenneth E. Dombrowski
- Subjects
Interleukin 2 ,Cancer Research ,Glycosylation ,medicine.medical_treatment ,Immunology ,Molecular Sequence Data ,Breast Neoplasms ,Biology ,Adenocarcinoma ,Peripheral blood mononuclear cell ,Natural killer cell ,medicine ,Tumor Cells, Cultured ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,Amino Acid Sequence ,Lymph node ,Pharmacology ,Ovarian Neoplasms ,Binding Sites ,Mucin ,Mucin-1 ,T lymphocyte ,Molecular biology ,digestive system diseases ,Peptide Fragments ,medicine.anatomical_structure ,Cytokine ,Mutagenesis ,Leukocytes, Mononuclear ,Female ,K562 Cells ,medicine.drug ,T-Lymphocytes, Cytotoxic - Abstract
MUC1 mucin peptides stimulated cytotoxic T lymphocytes (CTL) from humans with adenocarcinomas. Peripheral blood mononuclear cells, tumor-draining lymph node cells, or tumor-infiltrating lymphocytes were stimulated using mono-nuclear cells from humans with adenocarcinomas of breast or ovary, respectively, using (a) a native MUC1 mucin tandem repeat peptide of 20 amino acids (MUC1-mtr1) plus recombinant human interleukin-2 (IL-2), (b) the mutated (T3N) MUC1-mtr1 plus IL-2, or (c) immobilized anti-CD3 plus IL-2, or (d) IL-2 alone. The CTL stimulated by each of these four conditions were predominately CD4+. However, the CTL stimulated by either the native MUC1-mtr1 or (T3N) MUC1-mtr1 showed 5-10 times greater cytotoxicity of a breast cancer cell line that expresses MUC1 compared to CTL stimulated by either anti-CD3 + IL-2 or IL-2 alone. Each incubation condition generated CTL with different variable beta gene families of T-cell receptors, implying an oligoclonal expansion of a limited CTL repertoire for each. Thus, peptide-stimulated T cells showed expression of cytotoxic cells, which was not induced by nonspecific (anti-CD3 or IL-2) stimulation.
- Published
- 2000