The development of donor specific antibody is associated with graft rejection and increased mortality in solid organ transplant recipients. The majority of de novo donor specific antibodies (dnDSA) are against HLA-DQ antigens, but it has not been investigated if this is caused by more mismatches in the HLA-DQ locus between the recipient and donor. Here we examined the impact of HLA mismatches in eight HLA loci on the development of dnDSA and on rejection in a large cohort of heart transplant recipients. We evaluated HLA mismatches at the antigen level, the eplet level using HLAMatchmaker, and the epitope level using the PIRCHE algorithm. We found that the majority of dnDSA were against HLA-DQ antigens, and the number of dnDSA per mismatch is highest for HLA-DQ compared to other HLA loci. Furthermore, mismatches of HLA-DQ at the epitope level were associated with antibody-mediated rejection. Our results suggest that HLA mismatches at the HLA-DQ locus are more immunogenic than mismatches at other HLA loci to stimulate the development of dnDSA and to cause graft rejection.

供体特异性抗体的发展与实体器官移植接受者的移植排斥和死亡率增加有关。多数新生供体特异性抗体（dnDSA）针对HLA-DQ抗原，但是尚未研究是否这是由于受体和供体之间HLA-DQ基因座的更多错配引起的。在这里，我们检查了8个HLA基因座中HLA错配对dnDSA的发育以及大批心脏移植受者排斥反应的影响。我们在抗原水平，使用HLAMatchmaker的小蛋白水平和在PIRCHE算法的表位水平评估HLA错配。我们发现，大多数dnDSA都针对HLA-DQ抗原，与其他HLA基因座相比，HLA-DQ每个错配的dnDSA数量最高。此外，HLA-DQ在表位水平的错配与抗体介导的排斥有关。