Augmentation of immune response by an analog of the antigenic peptide in a human T-cell clone recognizing mutated Ras-derived peptides.

Abstract

T-cells that recognize mutated p21 Ras are relevant to immune surveillance systems against cancer. We report here evidence that immune responses of a T-cell clone recognizing mutated p21 Ras can be augmented by an analog peptide. Using spleen cells from a gastric cancer patient, we established the CD4+ alpha beta Th1-like clone C27 that recognizes wild-type (3EYKLVVVGAGGVGKS17) and mutated p21 Ras protein molecules and peptides, in an HLA-DR1-restricted manner. C27 responded prominently to mutated Ras peptides carrying Val or Ala at position 12, as compared to wild-type and other mutated peptides. C27 also exhibited a much stronger response to a mutated p21 Ras whole-protein molecule-carrying Val at position 12, as compared with the wild-type protein. The proliferative response and production of GM-CSF, TNF-alpha, and IFN-gamma by C27 were further augmented by replacing the possible first DR anchor 4Tyr of the mutated Ras peptide with Trp, a more potent anchor residue for the DR1 molecule. Enhancement of peptide antigenicity by substituting the HLA anchor residue of an antigenic peptide recognized by tumor-reactive T-cells may prove to be a novel strategy for antigen-specific cancer immunotherapy.

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@article{Yokomizo1997AugmentationOI, title={Augmentation of immune response by an analog of the antigenic peptide in a human T-cell clone recognizing mutated Ras-derived peptides.}, author={Hisashi Yokomizo and Sachio Matsushita and S Fujisao and Shinya Murakami and Hideki Fujita and Mikako Shirouzu and S. Yokoyama and M Ogawa and Yoshihiro Nishimura}, journal={Human immunology}, year={1997}, volume={52 1}, pages={22-32} }