Yokomizo H, Matsushita S, Fujisao S, Murakami S, Fujita H, Shirouzu M, Yokoyama S, Ogawa M, Nishimura Y
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Hum Immunol. 1997 Jan;52(1):22-32. doi: 10.1016/S0198-8859(96)00254-6.
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.
识别突变型p21 Ras的T细胞与针对癌症的免疫监视系统相关。我们在此报告证据表明，一种识别突变型p21 Ras的T细胞克隆的免疫反应可被一种类似肽增强。利用一名胃癌患者的脾细胞，我们建立了CD4+αβ Th1样克隆C27，该克隆以HLA-DR1限制的方式识别野生型（3EYKLVVVGAGGVGKS17）和突变型p21 Ras蛋白分子及肽段。与野生型和其他突变肽相比，C27对在第12位携带Val或Ala的突变Ras肽有显著反应。与野生型蛋白相比，C27对在第12位携带Val的突变型p21 Ras全蛋白分子也表现出更强的反应。通过将突变Ras肽可能的第一个DR锚定残基4Tyr替换为Trp（一种对DR1分子更有效的锚定残基），C27的增殖反应以及GM-CSF、TNF-α和IFN-γ的产生进一步增强。通过替换肿瘤反应性T细胞识别的抗原肽的HLA锚定残基来增强肽的抗原性，可能被证明是一种用于抗原特异性癌症免疫治疗的新策略。
