Liu Z, Williams K P, Chang Y H, Smith J A
Department of Molecular Biology, Massachusetts General Hospital, Boston.
J Immunol. 1993 Aug 15;151(4):1852-8.
The mechanism of immunodominance was studied by mutating a single amino acid residue within an immunodominant determinant of Staphylococcus aureus nuclease (Nase). Residues 81 to 100, which can be further reduced to 86 to 100, were determined to be the immunodominant determinant of Nase in H-2k mice. By introducing selected single amino acid substitutions into the peptide encompassing residues 86 to 100 (p86-100), residue 90 was shown to be one of the critical amino acids for T cell recognition, inasmuch as most of the T cells recognizing p86-100 do not respond to a p86-100 analog with a substitution of leucine for alanine at the residue 90. A mutant of Nase with a replacement of alanine by leucine at residue 90 (A90L) was constructed, and for A90L region 112 to 130, which is a subdominant determinant in Nase, becomes immunodominant. Although unable to respond to Nase, T cells primed in vivo with the peptides covering various cryptic determinants proliferate when challenged with A90L in vitro. Our results suggest that at the protein level there is competition among potential T cell determinants of protein Ag for binding to MHC molecules, and that this competition plays a role in determining which determinant may become immunodominant.
通过对金黄色葡萄球菌核酸酶（Nase）免疫显性决定簇内的单个氨基酸残基进行突变，研究了免疫显性机制。已确定81至100位残基（可进一步缩减为86至100位残基）是H-2k小鼠中Nase的免疫显性决定簇。通过将选定的单个氨基酸取代引入包含86至100位残基的肽（p86-100）中，发现90位残基是T细胞识别的关键氨基酸之一，因为大多数识别p86-100的T细胞对90位残基处亮氨酸取代丙氨酸的p86-100类似物无反应。构建了90位残基处丙氨酸被亮氨酸取代的Nase突变体（A90L），对于A90L，Nase中的次显性决定簇112至130区域变得具有免疫显性。尽管无法对Nase作出反应，但用覆盖各种隐蔽决定簇的肽在体内引发的T细胞在体外受到A90L刺激时会增殖。我们的结果表明，在蛋白质水平上，蛋白质抗原潜在的T细胞决定簇之间存在竞争以结合MHC分子，并且这种竞争在决定哪个决定簇可能成为免疫显性方面起作用。
