Drover S, Marshall W H, Kwok W W, Nepom G T, Karr R W
Faculty of Medicine, Memorial University of Newfoundland, Canada.
Scand J Immunol. 1994 Jun;39(6):539-50. doi: 10.1111/j.1365-3083.1994.tb03411.x.
A shared amino-acid sequence on the alpha helix of certain DR beta 1 chains is predicted to generate a 'shared epitope' that is implicated in susceptibility to the development of rheumatoid arthritis (RA). Different relative risks (RR) for disease susceptibility and severity conferred by these DR beta 1 chains suggest that their 'shared epitopes' are not equivalent. A set of monoclonal antibodies (MoAb) that map to the critical region, and for which optimal binding depends on DR context and cell lineage, was used to test this idea. Mapping experiments using mutated DR beta 1* molecules showed that the antibody-binding epitopes are overlapping; residue 70Q is pivotal for each, but neighbouring residues on the alpha helix and on the floor of the groove are also involved. Importantly, these epitopes are profoundly modified by peptide loading of DR beta 1*0401 molecules. These data suggest that 'shared epitopes' on DR molecules that are associated with RA are influenced by their context; such structural modifications may be the basis for the varying susceptibilities conferred by these DR molecules for the development of RA.
某些DRβ1链α螺旋上的一个共享氨基酸序列预计会产生一个“共享表位”，该表位与类风湿性关节炎（RA）发病的易感性有关。这些DRβ1链赋予疾病易感性和严重程度的不同相对风险（RR）表明它们的“共享表位”并不等同。一组定位到关键区域且最佳结合取决于DR背景和细胞谱系的单克隆抗体（MoAb）被用于验证这一想法。使用突变的DRβ1分子进行的定位实验表明，抗体结合表位相互重叠；70Q残基对每个表位都至关重要，但α螺旋上以及沟槽底部的相邻残基也有参与。重要的是，这些表位会因DRβ10401分子的肽负载而发生深刻改变。这些数据表明，与RA相关的DR分子上的“共享表位”会受其背景影响；这种结构修饰可能是这些DR分子赋予RA发病不同易感性的基础。
