Cytotoxic T lymphocytes from humans with adenocarcinomas stimulated by native MUC1 mucin and a mucin peptide mutated at a glycosylation site

MUC1 mucin peptides stimulated cytotoxic T lymphocytes (CTL) from humans wi th adenocarcinomas. Peripheral blood mononuclear cells, rumor-draining lymp h node cells, or tumor-infiltrating lymphocytes were stimulated using monon uclear cells from humans with adenocarcinomas of breast or ovary, respectiv ely, using (a) a native MUC1 mucin tandem repeat peptide of 20 amino acids (MUC1 -mtr(1)) plus recombinant human interleukin-2 (IL-2), (b) the mutated (T3N) MUC1-mtr, plus IL-2, or (c) immobilized anti-CD3 plus IL-2, or (d) I L-2 alone. The CTL stimulated by each of these four conditions were predomi nately CD4(+). However, the CTL stimulated by either the native MUC1-mtr(1) or (T3N) MUC1-mtr(1) showed 5-10 times greater cytotoxicity of a breast ca ncer cell line that expresses MUC1 compared to CTL stimulated by either ant i-CD3 + IL-2 or IL-2 alone. Each incubation condition generated CTL with di fferent variable beta gene families of T-cell receptors, implying an oligoc lonal expansion of a limited CTL repertoire fur each. Thus, peptide-stimula ted T cells showed expression of cytotoxic cells, which was not induced by nonspecific (anti-CD3 or IL-2) stimulation.