Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites.
Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites.
复制标题
DOI：
10.4049/jimmunol.147.5.1709
复制
发表时间：
1991-09
影响因子：
4.4
通讯作者：
E. Kabat;Te Wu Tai Te Wu-Te-Wu-Tai-Te-Wu-2244585577
中科院分区：
文献类型：
--
作者：
E. Kabat;Te Wu Tai Te Wu-Te-Wu-Tai-Te-Wu-2244585577
通过检查不同特异性抗体的氨基酸序列，我们发现许多明显不同特异性的抗体组装了相同的VL结构域和不同的VH结构域。相比之下，在不同特异性的抗体组中很少发现相同的VH结构域。我们鉴定了另外一组不同特异性和相同序列的抗体，覆盖氨基酸残基VH1至94和VL1至95。此外，还有一些额外的抗体片段无法获得完整的序列，但在VL CDR1、VL CDR2和VL CDR3中发现了直到VL-JL连接处的相同之处。有许多相同的VL1到95个片段具有不同的VH1到94序列，反之亦然，这一发现提出了关于VH在影响VL构象中的作用以及VL在影响VH构象中的作用的重要问题。还引用了证据表明，单一氨基酸的改变可能会严重破坏位点结构，在某些情况下会取消结合。我们的发现表明，未来利用X射线结晶学、核磁共振或其他方法进一步研究抗体构象对抗体结构的影响，以更好地了解抗体结合部位的功能和形态将是重要的。
By examining a large database of amino acid sequences of antibodies of various specificities, we have found that many antibodies of distinctly different specificities assemble identical VL domains with different VH domains. In contrast, rarely is the same VH domain found in sets of antibodies of different specificities. We identified additional sets of antibodies of different specificities and identical sequences covering amino acid residues VH 1 to 94 and VL 1 to 95. In addition, there were segments of additional antibodies for which complete sequences were not available, but identities were seen in VL CDR1, VL CDR2, and VL CDR3 up to the VL-JL junction. The finding that there are many identical VL 1 to 95 segments with different VH 1 to 94 sequences, and vice versa, raises important questions as to the role of VH in influencing the conformation of VL and, conversely, the role of VL in influencing the conformation of VH. Evidence is also cited indicating that a single amino acid change may seriously disrupt site structure and in some instances abolish binding. Our findings suggest that it will be important in the future to investigate further conformational effects on antibody structure by using X-ray crystallography, nuclear magnetic resonance spectroscopy, or other methods, to obtain a better understanding of the functions and topography of antibody-combining sites.