Specificity analyses of peptide binding to human leukocyte antigen (HLA)-A molecules have been hampered due to a lack of proper monoclonal antibodies (mAbs) for certain allomorphs, such as the prevalent HLA-A1 for Caucasians and HLA-A11 for Asians. We developed a mAb that recognizes a conformational epitope common to most HLA-A allomorphs. The mAb, named A-1, does not discriminate peptides by amino acid sequences, making it suitable for measuring peptide binding. A stabilization assay using TAP-deficient cell lines and A-1 was developed to investigate the specificity of peptide binding to HLA-A molecules. Regarding the evolution of HLA-A genes, the A-1 epitope has been conserved among most HLA-A allomorphs but was lost when the HLA-A gene diversified into the HLA-A*32, HLA-A*31, and HLA-A*33 lineages together with HLA-A*29 after bifurcating from the HLA-A*25 and HLA-A*26 branchs. The establishment of A-1 is expected to help researchers investigate the peptide repertoire and develop computational tools to identify cognate peptides. Since no HLA-A locus-specific mAb has been available, A-1 will also be useful for analyzing the locus-specific regulation of the HLA gene expression.

中文翻译：

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开发一种新型单克隆抗体，以依赖构象但肽混杂的方式与大多数 HLA-A 同种异形体结合。

由于缺乏针对某些同种异体的合适的单克隆抗体 (mAb)，例如白种人流行的 HLA-A1 和亚洲人流行的 HLA-A11，对结合人类白细胞抗原 (HLA)-A 分子的肽的特异性分析受到阻碍。我们开发了一种单克隆抗体，可识别大多数 HLA-A 同种异型体共有的构象表位。名为 A-1 的 mAb 不通过氨基酸序列区分肽，使其适用于测量肽结合。开发了使用 TAP 缺陷细胞系和 A-1 的稳定化分析，以研究肽与 HLA-A 分子结合的特异性。关于 HLA-A 基因的进化，A-1 表位在大多数 HLA-A 同种异形体中是保守的，但当 HLA-A 基因多样化为 HLA-A*32、HLA-A*31、从 HLA-A*25 和 HLA-A*26 分支分叉后，HLA-A*33 谱系与 HLA-A*29 一起。A-1 的建立有望帮助研究人员研究肽库并开发计算工具来识别同源肽。由于没有可用的 HLA-A 基因座特异性 mAb，A-1 也可用于分析 HLA 基因表达的基因座特异性调控。