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1996-02-26
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Document 0534
DOCN M9620534
TI Identification of an HLA-A11-restricted epitope from the tandem repeat
domain of the epithelial tumor antigen mucin.
DT 9602
AU Domenech N; Henderson RA; Finn OJ; Department of Molecular Genetics and
Biochemistry, University of; Pittsburgh School of Medicine, PA 15261,
USA.
SO J Immunol. 1995 Nov 15;155(10):4766-74. Unique Identifier : AIDSLINE
MED/96062294
AB Epithelial cell mucin encoded by the MUC-1 gene is overexpressed and
aberrantly glycosylated on pancreatic, breast, and ovarian cancers as
well as on multiple myelomas. It is recognized by patients' Ab and by T
cells derived from tumor-draining lymph nodes. The T cell recognition is
not MHC restricted and is specific for an epitope previously localized
to the immunodominant tandem repeat region of the native mucin molecule.
In search of possible MHC-restricted epitopes in the same immunodominant
region, we synthesized a panel of overlapping, nine-amino acid long
peptides spanning the MUC-1 tandem repeat and first examined their
binding to specific human MHC class I molecules using two independent
flow cytometry-based assay systems. This approach identified one
peptide, p9-17 (STAPPAHGV), that bound to HLA-A1, -A2.1, -A3, and -A11.
Measurements of the affinity of binding to each of these alleles, using
a quantitative molecular binding assay, indicated that only the relative
binding affinity to HLA-A11 was close to immunogenic values. We tested
the immunogenicity of p9-17 in vitro. We detected a secondary T cell
response specific for p9-17 in lymph nodes from an HLA-A11 breast cancer
patient. Moreover, CTL specific for p9-17 peptide could be generated
from PBL in several healthy HLA-A11 donors by primary in vitro
stimulation.
DE Amino Acid Sequence Cytotoxicity, Immunologic CD8-Positive
T-Lymphocytes/*IMMUNOLOGY Epithelium/IMMUNOLOGY/PATHOLOGY
Epitopes/*CHEMISTRY/IMMUNOLOGY Human HLA-A
Antigens/CHEMISTRY/*IMMUNOLOGY Molecular Sequence Data
Mucins/CHEMISTRY/*IMMUNOLOGY Peptides/CHEMISTRY/CHEMICAL SYNTHESIS
Repetitive Sequences, Nucleic Acid Sequence Analysis Support, Non-U.S.
Gov't Support, U.S. Gov't, P.H.S. Tumor Cells, Cultured JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).