Human T lymphocytes recognize a peptide of single point-mutated, oncogenic ras proteins.
P21ras proteins are thought to play an important role in cell proliferation and differentiation. Single nucleotide mutations in the encoding cellular proto-oncogenes often result in p21ras proteins with transforming activity. Such activated ras oncogenes have been demonstrated in a variety of human malignancies and also in preneoplastic changes. Using a synthetic peptide corresponding to amino acids 5-16 of mutated p21ras proteins with an exchange of the normal glycine at position 12 by valine, it is shown here that human CD4+ T cells specifically recognize the mutated protein sequence and can be generated as antigen-specific T lymphocyte lines. The fact that these T lines did not crossreact to the sequence of normal p21ras proteins offers new perspectives for specific immunotherapy of human malignancies and even precancerous lesions.
Jung
S
S
Department of Neurology, University of Würzburg, Federal Republic of Germany.
Schluesener
H J
HJ
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006681:HLA-D Antigens / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D006681:HLA-D Antigens; D010446:Peptide Fragments; D015689:Oncogene Protein p21(ras)