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 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.
Wright
S E
SE
Department of Veterans Affairs Medical Center, Amarillo, USA.
Kilinski
L
L
Talib
S
S
Lowe
K E
KE
Burnside
J S
JS
Wu
J Y
JY
Dolby
N
N
Dombrowski
K E
KE
Lebkowski
J S
JS
Philip
R
R
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology*; D005260:Female; D006031:Glycosylation; D006801:Humans; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D016296:Mutagenesis; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments