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

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