Kieber-Emmons T, Foster M H, Williams W V, Madaio M P
Wistar Institute of Biology and Anatomy, University of Pennsylvania, Philadelphia, USA.
Immunol Res. 1994;13(2-3):172-85. doi: 10.1007/BF02918278.
Structural analysis of lupus autoantibodies is beginning to provide clues to the molecular basis for antigenic specificity and pathogenicity. The present analysis indicates that multiple light and heavy chains contain residues which can facilitate DNA binding, reaffirming the notion that there are multiple ways that different amino acids combine to form an antigen-binding pocket with affinity for dsDNA and ssDNA. Furthermore, this analysis suggests that these conformations and contact residues are intrinsic to germline sequences, although amino acid changes at critical locations (somatically introduced) modulate antigen binding, and appear to influence the capacity of individual immunoglobulin to form immune deposits. Analysis of additional individual immunoglobulins with closely related V-region sequences and differing pathogenic properties will be required to resolve the contribution of specific motifs to pathogenecity.
狼疮自身抗体的结构分析开始为抗原特异性和致病性的分子基础提供线索。目前的分析表明，多条轻链和重链含有可促进DNA结合的残基，再次证实了不同氨基酸以多种方式组合形成对双链DNA和单链DNA具有亲和力的抗原结合口袋这一观点。此外，该分析表明，尽管关键位置（体细胞引入）的氨基酸变化会调节抗原结合，并似乎影响单个免疫球蛋白形成免疫沉积物的能力，但这些构象和接触残基对于种系序列来说是内在的。需要对具有密切相关V区序列和不同致病特性的更多个体免疫球蛋白进行分析，以确定特定基序对致病性的贡献。
