Institut für Immungenetik, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Thielallee 73, 14195 Berlin, Germany.
Curr Opin Rheumatol. 2013 Jul;25(4):411-8. doi: 10.1097/BOR.0b013e32836203ab.
The differential association of HLA-B27 subtypes with ankylosing spondylitis provides the rationale for a comparative investigation of these proteins. Results from the last 2 years of research on minimally distinct HLA-B27 subtypes, primarily using biochemical and biophysical techniques, are presented and discussed.
We summarize evidence that micropolymorphisms within the molecules' peptide-binding groove influence wide-ranging biochemical, biophysical and antigenic properties of HLA-B27 molecules, and suggest that distinct, subtype and peptide-dependent dynamics of peptide - heavy chain - β(2)-microglobulin heterotrimers could be instrumental for an understanding of the initiation of disease processes that are connected with certain HLA-B27 subtypes.
The results indicate that mAbs that bind only to structurally distinguishable subsets of HLA-B27 molecules as well as techniques that assess the flexibility of these antigens may hold the key to comprehend molecular events contributing to the initial stages of disease pathogenesis in spondyloarthropathies.
不同的 HLA-B27 亚型与强直性脊柱炎的关联为这些蛋白的对比研究提供了依据。本文主要介绍和讨论了过去两年间关于 HLA-B27 亚型的研究结果,这些研究主要采用了生化和生物物理技术。
我们总结了证据表明分子肽结合槽内的微多态性影响 HLA-B27 分子的广泛生化、生物物理和抗原特性,并提出肽-重链-β(2)-微球蛋白异三聚体的不同亚型和肽依赖性动力学可能对于理解与某些 HLA-B27 亚型相关的疾病发生过程的起始具有重要意义。
这些结果表明,仅与结构可区分的 HLA-B27 分子亚群结合的 mAbs 以及评估这些抗原的灵活性的技术可能是理解导致脊柱关节病发病机制初始阶段的分子事件的关键。