EPITOPE FINE SPECIFICITY OF HUMAN ANTI-HLA-A2 ANTIBODIES - IDENTIFICATION OF 4 EPITOPES INCLUDING A HAPTEN-LIKE EPITOPE ON HLA-A2 AT LYSINE 127
EPITOPE FINE SPECIFICITY OF HUMAN ANTI-HLA-A2 ANTIBODIES - IDENTIFICATION OF 4 EPITOPES INCLUDING A HAPTEN-LIKE EPITOPE ON HLA-A2 AT LYSINE 127
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DOI：
10.1016/0198-8859(93)90182-z
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发表时间：
1993-07-01
期刊：
影响因子：
2.7
通讯作者：
BURLINGHAM, WJ
中科院分区：
文献类型：
--
作者：
DEVITO, LD;MASON, BP;BURLINGHAM, WJ
通过亲和层析法从7个个体中纯化出抗hla - a2 CREG抗体。纯化后的抗体与HLA-A2.1的单个或多个氨基酸变体的结合用抑制RIA测定。在多态α 1和α 2结构域的10个氨基酸残基上的替换对于人抗体的结合是重要的；其中8个先前已被证明在小鼠抗hla - a2 CREG抗体的结合中起重要作用。与先前报道的任何小鼠单克隆抗体不同，来自两个个体的抗体的结合被HLA-A2， -24， -28共享环氨基酸残基赖氨酸127的替换所消除。相反，当非交叉反应性HLA-A3上残基127处的天门汀被赖氨酸取代时，抗体结合完全恢复。结果进一步表明，结合该区域的含有lambda-和kappa-的人抗体可能将赖氨酸127识别为半抗原样表位。识别由α 1结构域甘氨酸62改变定义的构象表位的抗hla - a2抗体以λ轻链为主，而识别由α 2结构域色氨酸107环残基定义的表位的抗hla - a2抗体以kappa轻链为主。这些数据与人类B细胞对HLA- a2的限制性表位识别模型一致，该模型与小鼠B细胞杂交瘤的表位识别相似，但不同，并且可能有助于解释HLA系统中公共或交叉反应的独特型现象。
Anti-HLA-A2 CREG antibodies were purified from seven individuals by affinity chromatography. The binding of the purified antibodies to single or multiple amino acid variants of HLA-A2.1 was measured with an inhibition RIA. Substitutions at 10 amino acid residues in the polymorphic alpha1 and alpha2 domains were important for human antibody binding; eight of these have previously been shown to be important in the binding of murine anti-HLA-A2 CREG antibodies. Unlike any previously reported murine mAbs, the binding of antibodies from two individuals was eliminated by a substitution at the HLA-A2, -24, -28 shared loop amino acid residue lysine 127. Conversely, when the asparagine at residue 127 on the non-cross-reactive HLA-A3 was replaced with lysine, antibody binding was completely restored. The results further suggest that both lambda- and kappa-containing human antibodies that bind to this region may recognize lysine 127 as a haptenlike epitope. Anti-HLA-A2 antibodies that recognized a conformational epitope defined by changes at glycine 62 in the alpha1 domain were predominanted by lambda light chains whereas those that recognize an epitope defined by a loop residue at tryptophan 107 in the alpha2 domain were predominated by kappa light chains. The data are consistent with a model of restricted epitope recognition of HLA-A2 by human B cells that is similar to, but distinct from, epitope recognition by mouse B-cell hybridomas, and may help to explain the phenomenon of public or cross-reactive idiotypes in the HLA system.