HLA-A蛋白的拓扑结构增强了移植受者共享和趋同的免疫显性B细胞和抗体同种异体反应，这一成果由阿拉巴马大学伯明翰分校希尔辛克医学院Frances E. Lund研究小组经过不懈努力而取得。该项研究成果发表在2025年11月24日出版的《免疫学》上。

该研究团队侧写了HLA-A01:01特异性B细胞反应在接受抗体介导的排斥反应的移植肾和血液中，并在同种免疫反应早期发现免疫优势B细胞和抗体反应。这些反应集中在位于HLA-A*01:01肽结合槽α螺旋中的拓扑暴露的错配HLA残基上。研究团队证明了在HLA-A01:01不匹配的移植受者的不同群体中，抗HLA-A01:01B细胞同种异体反应收敛并维持在相同的免疫显性HLA亚区，该亚区仅占HLA分子的20%。因此，B细胞和抗体的同种异体反应似乎紧密地集中在HLA-A01:01冠在个体之间是保守的表达不同的自我HLA-A星座。

据介绍，移植供体和受体之间针对人类白细胞抗原（HLA）蛋白的供体特异性抗体反应不匹配，然而同种异体移植物丢失，同种异体反应性B细胞和抗体靶向的HLA结构表位在很大程度上仍未解决。

附：英文原文

Title: Topography of the HLA-A protein enforces shared and convergent immunodominant B cell and antibody alloresponses in transplant recipients

Author: John T. Killian, R. Glenn King, Aaron C.K. Lucander, James L. Kizziah, Christopher F. Fucile, Ruben Diaz-Avalos, Shihong Qiu, Aaron Silva-Sanchez, Betty J. Mousseau, Kevin J. Macon, Amanda R. Callahan, Guang Yang, M. Emon Hossain, Jobaida Akther, Daryl B. Good, Susan Kelso, Julie A. Houp, Frida Rosenblum, Paige M. Porrett, Song C. Ong, Vineeta Kumar, Erica Ollmann Saphire, John F. Kearney, Troy D. Randall, Alexander F. Rosenberg, Todd J. Green, Frances E. Lund

Issue&Volume: 2025-11-24

Abstract: Donor-specific antibody responses against human leukocyte antigen (HLA) proteins mismatched between transplant donors and recipients cause allograft loss, yet the structural HLA epitopes targeted by alloreactive B cells and antibodies remain largely unresolved. We profiled the HLA-A01:01-specific B cell response in the transplanted kidney and blood of a recipient undergoing antibody-mediated rejection and identified immunodominant B cell and antibody responses that emerged early in the alloimmune response. These responses were focused on topographically exposed mismatched HLA residues located in the α helices along the peptide-binding groove of HLA-A01:01. We demonstrated that the anti-HLA-A01:01 B cell alloresponse converged and was maintained on this same immunodominant HLA subregion, which comprises only 20% of the HLA molecule, in a diverse group of HLA-A01:01-mismatched transplant recipients. Thus, the B cell and antibody alloresponses appear tightly focused on a topographically defined region on the HLA-A01:01 crown that is conserved across individuals expressing distinct constellations of self-HLA-A.

DOI: 10.1016/j.immuni.2025.10.014

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00466-2