Sun J, Takahashi N, Kakinuma H, Nishi Y
Laboratory of Life Science and Biomolecular Engineering, Japan Tobacco, Yokohama, Kanagawa, Japan.
J Immunol. 2001 Nov 15;167(10):5775-85. doi: 10.4049/jimmunol.167.10.5775.
Catalytic Abs (catAbs) preferentially evolved in autoimmune MRL/MPJ-lpr/lpr (MRL/lpr) mice upon immunization with the phosphonate transition-state analogue (TSA), but this did not happen in normal BALB/c mice. The majority of the catAbs from MRL/lpr mice were from several independent clones of the same family. Most of them had a lysine at position 95 in the heavy chain (H95), which is at the junctional region. This residue, which interacts with the phosphonate moiety of the TSA and presumably is involved in the catalytic activity, was not changed even after expansive evolution following multiple mutations. By contrast, the majority that arose from BALB/c mice were the non-catAbs, which were quite different in the sequence from the catAbs from MRL/lpr mice, but they were clonally related to one another, so most of them were originated from a single clone. In the MRL/lpr mice, the catalytic subsets that existed in the initial repertoire were effectively captured by the phosphonyl oxygens in the TSA by interacting with the lysine at H95. In the BALB/c mice, however, another noncatalytic subset with only the binding capability directed to a moiety other than the phosphonate moiety was alternatively evolved, because of the lowest abundance or elimination of the catalytic subsets.
在用膦酸酯过渡态类似物（TSA）免疫后，催化性抗体（catAbs）优先在自身免疫性MRL/MPJ-lpr/lpr（MRL/lpr）小鼠中产生，但正常BALB/c小鼠中不会出现这种情况。来自MRL/lpr小鼠的大多数catAbs来自同一家族的几个独立克隆。它们中的大多数在重链的第95位（H95）有一个赖氨酸，该位置位于连接区。这个残基与TSA的膦酸酯部分相互作用，可能参与催化活性，即使在多次突变后的广泛进化后也没有改变。相比之下，来自BALB/c小鼠的大多数是非催化性抗体（non-catAbs），它们在序列上与来自MRL/lpr小鼠的catAbs有很大不同，但它们彼此克隆相关，所以大多数都起源于单个克隆。在MRL/lpr小鼠中，初始库中存在的催化亚群通过与H95处的赖氨酸相互作用，被TSA中的磷酰氧有效地捕获。然而，在BALB/c小鼠中，由于催化亚群的丰度最低或被消除，另一个仅对膦酸酯部分以外的部分具有结合能力的非催化亚群被选择性地进化出来。
