Fu X T, Klohe E, Alber C, Yu W Y, Ferrara G B, Pistillo M P, Ballas M, Karr R W
Department of Veterans Affairs Medical Center, Iowa City, Iowa.
Hum Immunol. 1992 Mar;33(3):193-201. doi: 10.1016/0198-8859(92)90071-t.
In a previous study, we used transfectants expressing hybrid HLA-DR(beta 10403)/DR(beta 10701) chains to map sequences involved in polymorphic antibody binding epitopes on DR(alpha, beta 10403) or DR(alpha, beta 10701) molecules. Amino acids 1-40 of the beta 1 domain were found to make the major contributions to most of the antibody binding epitopes studied. To begin to localize sequences that contribute to polymorphic antibody epitopes on DR(alpha,beta 10101), DR(alpha,beta 11101) and DR(alpha,beta 30202) molecules, we used indirect immunofluorescence and flow cytometry to assess the binding of mAb to transfectants expressing hybrid DR(beta 10101)/DR(beta 11101) or DR(beta 11101)/DR(beta 30202) chains that divide the DR beta chain into three segments: amino acids 1-40, 41-97, and the beta 2 domain. The results indicate that amino acids 41-97 of the beta 1 domain on DR(beta 10101), DR(beta 11101), or DR(beta 30202) are critical in most of the epitopes, including those recognized by human antibodies MP4 and MP12, and mouse mAb GS88.2, I-LR1, 21r5, and 7.3.19.1, whereas amino acids 1-40 of DR(beta 11101) are critical in the epitope recognized by the MCS-7 mAb, and both segments 1-40 and 41-97 of DR(beta 11101) are important in the epitopes recognized by the I-LR2 and UL-52 mAbs. Based on these data and comparison of DR beta allelic protein sequences, the residues that may play critical roles in these antibody binding epitopes are predicted.
在之前的一项研究中，我们使用表达杂交HLA - DR(β10403)/DR(β10701)链的转染子来定位DR(α,β10403)或DR(α,β10701)分子上多态性抗体结合表位所涉及的序列。发现β1结构域的第1 - 40位氨基酸对所研究的大多数抗体结合表位起主要作用。为了开始定位DR(α,β10101)、DR(α,β11101)和DR(α,β30202)分子上对多态性抗体表位有贡献的序列，我们使用间接免疫荧光和流式细胞术来评估单克隆抗体与表达杂交DR(β10101)/DR(β11101)或DR(β11101)/DR(β30202)链的转染子的结合情况，这些杂交链将DRβ链分为三个区段：第[具体数字]位氨基酸，第41 - 97位氨基酸，以及β2结构域。结果表明，DR(β10101)、DR(β11101)或DR(β30202)上β1结构域的第41 - 97位氨基酸在大多数表位中起关键作用，包括那些被人源抗体MP4和MP12以及小鼠单克隆抗体GS88.2、I - LR1、21r5和7.3.19.1识别的表位；而DR(β11101)的第1 - 40位氨基酸在被MCS - 7单克隆抗体识别的表位中起关键作用，DR(β11101)的第1 - 40位和第41 - 97位区段在被I - LR2和UL - 52单克隆抗体识别的表位中都很重要。基于这些数据以及DRβ等位基因蛋白序列的比较，预测了在这些抗体结合表位中可能起关键作用的残基。
