Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Transplantation Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
HLA. 2021 Jan;97(1):30-43. doi: 10.1111/tan.14110. Epub 2020 Oct 28.
Eplets are defined as distinct amino acid configurations on the surface of HLA molecules. The aim of this study was to estimate the immunogenicity of HLA-DQ eplets in a cohort of 221 pregnancies with HLA-DQ mismatches. We defined the immunogenicity of an eplet by the frequency of antibody responses against it. Around 90% of all listed DQB1 or DQA1 eplets were at least five times mismatched and thus included for the calculation of their immunogenicity. The DQB1 eplets with the five highest immunogenicity scores were 55PP, 52PR, 52PQ, 85VG and 45EV; 25% of all DQB1 eplets were not reacting. The DQA1 eplets with the five highest immunogenicity scores were 25YS, 47QL, 55RR, 187T and 18S; 17% of all DQA1 eplets were not reacting. The immunogenicity score had a slightly higher area under the curve to predict development of child-specific antibodies than various molecular mismatch scores (eg, eplet mismatch load, amino acid mismatch load). Overlapping eplets were identified as a barrier to unambiguously assign the immunogenicity score based on HLA antibody reaction patterns. In this conceptual study, we explored the immunogenicity of HLA-DQ eplets and created a map of potentially immunogenic regions on HLA-DQ molecules, which requires validation in clinical transplant cohorts.
表位是指 HLA 分子表面上独特的氨基酸构型。本研究的目的是在 221 例 HLA-DQ 错配的妊娠队列中估计 HLA-DQ 表位的免疫原性。我们通过针对它的抗体反应频率来定义表位的免疫原性。大约 90%的所有列出的 DQB1 或 DQA1 表位至少有五倍错配，因此包括在计算它们的免疫原性中。免疫原性评分最高的五个 DQB1 表位是 55PP、52PR、52PQ、85VG 和 45EV；25%的 DQB1 表位没有反应。免疫原性评分最高的五个 DQA1 表位是 25YS、47QL、55RR、187T 和 18S；17%的 DQA1 表位没有反应。免疫原性评分预测儿童特异性抗体的发展比各种分子错配评分（例如表位错配负荷、氨基酸错配负荷）具有略高的曲线下面积。重叠表位被确定为根据 HLA 抗体反应模式明确分配免疫原性评分的障碍。在这项概念研究中，我们探索了 HLA-DQ 表位的免疫原性，并创建了 HLA-DQ 分子上潜在免疫原性区域的图谱，这需要在临床移植队列中进行验证。
