p53, a potential target for tumor-directed T cells.
Cell lineage-specific cellular proteins, oncogenes from viral or cellular origin and tumor suppressor genes encode tumor-specific/associated antigens. Such antigens can elicit an major compatibility complex (MHC) class I-restricted cytotoxic T lymphocyte (CTL) response, either naturally in cancer patients or following appropriate immunostimulation (in vitro or in vivo). The reported immune responses in humans to the melanoma-associated MAGE gene products, GP100 and tyrosinase, all self-proteins, support the idea to use wild-type p53 products as targets for T cells. An important step towards this goal is identification of potential p53 CTL epitopes. We identified the wild-type p53 peptides with the highest affinity to the HLA-A*0201 molecule using two assays: the previously described MHC peptide-binding assay and the peptide competition assay. We obtained CTL against four p53 peptides with a high affinity for the HLA-A*0201 molecule. These findings are discussed next to a short review concerning the p53 literature.
Nijman
H W
HW
Department of Immunohaematology and Blood Bank, University Hospital, Leiden, The Netherlands.
Van der Burg
S H
SH
Vierboom
M P
MP
Houbiers
J G
JG
Kast
W M
WM
Melief
C J
CJ
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002478:Cells, Cultured; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D007158:Immunologic Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000276:immunology*
D015234:HLA-A Antigens; D009842:Oligopeptides; D016159:Tumor Suppressor Protein p53