Document 0108
 DOCN  M9580108
 TI    Induction and characterization of cytotoxic T-lymphocytes recognizing a
       mutated p21ras peptide presented by HLA-A*0201.
 DT    9506
 AU    Van Elsas A; Nijman HW; Van der Minne CE; Mourer JS; Kast WM; Melief CJ;
       Schrier PI; Department of Clinical Oncology, University Hospital,
       Leiden, The; Netherlands.
 SO    Int J Cancer. 1995 May 4;61(3):389-96. Unique Identifier : AIDSLINE
       MED/95247335
 AB    The ras oncogene is frequently found to be activated in human cancer
       through point mutations at codons 12, 13 or 61. We explored whether
       these altered p21ras protein sequences contain peptide sequences that
       can activate naive CD8+ cytotoxic T lymphocytes (CTL). Several wild-type
       and mutated p21ras peptides were identified that carry a binding motif
       for human leukocyte antigen (HLA)-A*0201. Two peptides were found to
       bind strongly to this allele. CD8+ CTL bulk cultures specifically
       reacting with one of these peptides could be induced, using
       processing-defective T2 cells loaded with peptide CLLDILDTAGL as
       stimulators. The peptide is derived from p21ras, position 51-61, and
       carries a 61 Gln-->Leu mutation. In contrast, a 9-mer peptide CLLDILDTA
       corresponding to amino acid sequence 51-59 of wild-type p21ras did not
       yield reactive CTL cultures. T-cell clones with low affinity for the
       11-mer peptide were isolated from CLLDILDTAGL-reactive bulk cultures.
       These T cells did not lyse melanoma cells transfected with 61-Leu N-ras,
       although lysis was found when these transfectants were pulsed with the
       11-mer peptide. Possibly, T cells of higher affinity may be required to
       demonstrate processed peptide on the cell surface. The combined
       experiments suggest that a peptide derived from mutated p21ras can be
       recognized by HLA class I-restricted CTL, whereas an analogous wild-type
       p21ras peptide may not be immunogenic.
 DE    Alleles  Amino Acid Sequence  Cell Line  Comparative Study
       *Cytotoxicity, Immunologic  CD8-Positive T-Lymphocytes/*IMMUNOLOGY
       Human  HLA-A Antigens/*IMMUNOLOGY/METABOLISM  Kinetics  Leukemia,
       Myeloid, Chronic  Melanoma  Molecular Sequence Data  Peptide
       Fragments/*IMMUNOLOGY/METABOLISM  Protein Binding  Proto-Oncogene
       Protein p21(ras)/*IMMUNOLOGY/METABOLISM  Recombinant
       Proteins/IMMUNOLOGY/METABOLISM  Support, Non-U.S. Gov't  T-Lymphocytes,
       Cytotoxic/*IMMUNOLOGY  Transfection  Tumor Cells, Cultured  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).