PMID- 7729952
OWN - NLM
STAT- MEDLINE
DCOM- 19950601
LR  - 20190708
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 61
IP  - 3
DP  - 1995 May 4
TI  - Induction and characterization of cytotoxic T-lymphocytes recognizing a mutated 
      p21ras peptide presented by HLA-A*0201.
PG  - 389-96
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.
FAU - Van Elsas, A
AU  - Van Elsas A
AD  - Department of Clinical Oncology, University Hospital, Leiden, The Netherlands.
FAU - Nijman, H W
AU  - Nijman HW
FAU - Van der Minne, C E
AU  - Van der Minne CE
FAU - Mourer, J S
AU  - Mourer JS
FAU - Kast, W M
AU  - Kast WM
FAU - Melief, C J
AU  - Melief CJ
FAU - Schrier, P I
AU  - Schrier PI
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (HLA-A Antigens)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line
MH  - *Cytotoxicity, Immunologic
MH  - HLA-A Antigens/*immunology/metabolism
MH  - Humans
MH  - Kinetics
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive
MH  - Melanoma
MH  - Molecular Sequence Data
MH  - Peptide Fragments/*immunology/metabolism
MH  - Protein Binding
MH  - Proto-Oncogene Proteins p21(ras)/*immunology/metabolism
MH  - Recombinant Proteins/immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1995/05/04 00:00
MHDA- 1995/05/04 00:01
CRDT- 1995/05/04 00:00
PHST- 1995/05/04 00:00 [pubmed]
PHST- 1995/05/04 00:01 [medline]
PHST- 1995/05/04 00:00 [entrez]
AID - 10.1002/ijc.2910610319 [doi]
PST - ppublish
SO  - Int J Cancer. 1995 May 4;61(3):389-96. doi: 10.1002/ijc.2910610319.