Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Pathology and Laboratory Medicine Service, VA Connecticut Healthcare System, West Haven, Connecticut, USA.
Transfusion. 2022 Nov;62(11):2349-2362. doi: 10.1111/trf.17110. Epub 2022 Oct 7.
The immunogenicities of polypeptide blood group antigens vary, despite most being created by single amino acid (AA) substitutions. To study the basis of these differences, we employed an immunoinformatics approach to determine whether AA substitution sites of blood group antigens have structural features typical of B-cell epitopes and whether the extent of B-cell epitope properties is positively related to immunogenicity.
Fifteen structural property prediction programs were used to determine the likelihood of β-turns, surface accessibility, flexibility, hydrophilicity, particular AA composition and AA pairs, and other B-cell epitope properties at AA substitution sites of polypeptide blood group antigens.
AA substitution sites of Lu , Jk , E, c, M, Fy , C, and S were each located in regions with at least two structural features typical of B-cell epitopes. The substitution site of K, the most immunogenic non-ABO/D antigen, scored the lowest for most B-cell epitope properties and was the only one not predicted to be part of a linear B-cell epitope. The most immunogenic antigens studied (K, Jk , Lu , E) had B-cell epitope structural properties determined by the fewest programs; the least immunogenic antigens (e.g., Fy , S, C, c) had B-cell epitope properties according to the most programs.
Counter to prediction, the immunogenicity of polypeptide blood group antigens was not positively related to B-cell epitope structural features present at their AA-substitution sites. Instead, it tended to be negatively related. The AA-substitution site of the most immunogenic non-ABO/D antigen, K, had the least B-cell epitope features.
尽管大多数血型抗原的免疫原性是由单个氨基酸（AA）取代产生的，但它们的免疫原性却各不相同。为了研究这些差异的基础，我们采用免疫信息学方法来确定血型抗原的 AA 取代位点是否具有 B 细胞表位的结构特征，以及 B 细胞表位特性的程度是否与免疫原性呈正相关。
使用了 15 种结构性质预测程序来确定多肽血型抗原的 AA 取代位点处β-转角、表面可及性、柔韧性、亲水性、特定 AA 组成和 AA 对以及其他 B 细胞表位特性的可能性。
Lu、Jk、E、c、M、Fy、C 和 S 的 AA 取代位点分别位于至少具有两个 B 细胞表位典型结构特征的区域。最具免疫原性的非 ABO/D 抗原 K 的取代位点在大多数 B 细胞表位特性方面得分最低，并且是唯一未预测为线性 B 细胞表位的部分。研究中最具免疫原性的抗原（K、Jk、Lu、E）的 B 细胞表位结构特性由最少的程序确定；最具免疫原性的抗原（例如，Fy、S、C、c）的 B 细胞表位特性则由最多的程序确定。
与预测相反，多肽血型抗原的免疫原性与 AA 取代位点的 B 细胞表位结构特征没有正相关关系。相反，它往往呈负相关。最具免疫原性的非 ABO/D 抗原 K 的 AA 取代位点具有最少的 B 细胞表位特征。
