Liu Z R, Williams K P, Chang Y H, Smith J A
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
J Immunol. 1991 Jan 15;146(2):438-43.
The effect of amino acid residues outside of T cell determinant regions of Staphylococcus aureus nuclease (Nase) on the activation of T cell hybridomas has been investigated. T cell hybridomas derived from BALB/c mice immunized with Nase were screened against a nested set of overlapping synthetic peptides spanning the entire Nase molecule. Five regions of Nase, encompassing residues 1 to 20, 21 to 40, 61 to 80, 101 to 120, and 112 to 130, were found to be the T cell determinants. Region 61 to 80 is the immunodominant site. Mutants of Nase with a single amino acid substitution outside the defined T cell determinants were tested for their ability to stimulate the T cell hybridomas. The substitution of arginine for glutamic acid at residue 43 markedly reduces the antigenic potency of the protein for I-Ed restricted T cell hybridomas, which recognize Nase peptides comprised of residues 21 to 40 (p21-40) or 112 to 130 (p112-130). In contrast, the stimulatory capacity of this mutant for I-Ad restricted T cell hybridomas remains unchanged. Our results suggest that selective regulation of an immune response may be achieved by appropriately mutagenizing protein Ag.
已经研究了金黄色葡萄球菌核酸酶（Nase）T细胞决定簇区域外的氨基酸残基对T细胞杂交瘤激活的影响。用Nase免疫的BALB/c小鼠来源的T细胞杂交瘤，针对一组覆盖整个Nase分子的重叠合成肽进行筛选。发现Nase的五个区域，即包含第1至20位、21至40位、61至80位、101至120位和112至130位残基的区域，是T细胞决定簇。61至80位区域是免疫显性位点。对在确定的T细胞决定簇外有单个氨基酸替代的Nase突变体，测试其刺激T细胞杂交瘤的能力。在第43位残基处用精氨酸替代谷氨酸，显著降低了该蛋白对I-Ed限制性T细胞杂交瘤的抗原效力，这些杂交瘤识别由第21至40位残基（p21-40）或112至130位残基（p112-130）组成的Nase肽。相反，该突变体对I-Ad限制性T细胞杂交瘤的刺激能力保持不变。我们的结果表明，通过对蛋白质抗原进行适当诱变，可能实现免疫反应的选择性调节。
