Swine Xenografts Share Few Predicted Indirectly Recognisable SLA-Derived Epitopes With HLA-Derived Epitopes From Human Kidney Grafts

IF 5.9 4区 医学 Q2 CELL BIOLOGY
HLA Pub Date : 2025-06-21 DOI:10.1111/tan.70291
Benedict M. Matern, Eric Spierings, Emma Peereboom, Matt Tector, Joseph Tector, Massimo Mangiola, Robert A. Montgomery, Matthias Niemann
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Abstract

Swine-derived kidneys are a promising alternative organ source for transplantation, but compatibility in the major histocompatibility complex remains an immunological barrier. Furthermore, in repeat transplantations, CD4+ memory T cells can lead to a more rapid immune response against repeated exposure to the same antigens. Several studies have shown that HLA and SLA proteins share overlapping B cell epitopes due to structural or electrostatic similarities, but the role of overlapping T cell epitopes has not been fully explored. This study aims to computationally analyse the potential risk of memory T cell activation in subsequent human-after-swine and swine-after-human transplantation by evaluating shared T cell epitopes between the two graft sources. We show that while HLA and SLA demonstrate striking structural similarities, their linear protein sequences are very distinct, which translates to disparate HLA- and SLA-derived peptidomes and T cell epitopes. By applying the PIRCHE-II Tmem analysis to a simulated panel of recipients receiving repeat transplantations from a human kidney and from a swine xenograft, we observed a median of 1 shared T cell epitope in the cross-species context, compared to a median of 17 shared between two human-derived kidneys. This suggests that a swine xenograft exposes a low risk of T cell memory against a later human donor, and that xenotransplantation may provide an opportunity to receive a graft for highly HLA-sensitised recipients.

Abstract Image

猪异种移植物与人肾移植物的hla衍生表位几乎没有预测的可间接识别的sla衍生表位
猪源肾是一种很有前途的移植器官来源,但主要组织相容性复合体的相容性仍然是一个免疫障碍。此外,在重复移植中,CD4+记忆T细胞可以对重复暴露于相同抗原产生更快速的免疫反应。一些研究表明,HLA和SLA蛋白由于结构或静电相似性而具有重叠的B细胞表位,但重叠的T细胞表位的作用尚未得到充分探讨。本研究旨在通过评估两种移植来源之间共享的T细胞表位,计算分析记忆T细胞激活在随后的人-猪和猪-人移植中的潜在风险。我们发现,虽然HLA和SLA表现出惊人的结构相似性,但它们的线性蛋白序列非常不同,这转化为不同的HLA和SLA衍生的肽段和T细胞表位。通过将PIRCHE-II Tmem分析应用于接受人类肾脏和猪异种移植重复移植的模拟受体,我们观察到跨物种背景下共享1个T细胞表位的中位数,而两个人类肾脏共享的中位数为17个。这表明,猪异种移植对后来的人类供体暴露出较低的T细胞记忆风险,并且异种移植可能为高度hla敏感的受者提供接受移植物的机会。
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来源期刊
HLA
HLA Immunology and Microbiology-Immunology
CiteScore
3.00
自引率
28.80%
发文量
368
期刊介绍: HLA, the journal, publishes articles on various aspects of immunogenetics. These include the immunogenetics of cell surface antigens, the ontogeny and phylogeny of the immune system, the immunogenetics of cell interactions, the functional aspects of cell surface molecules and their natural ligands, and the role of tissue antigens in immune reactions. Additionally, the journal covers experimental and clinical transplantation, the relationships between normal tissue antigens and tumor-associated antigens, the genetic control of immune response and disease susceptibility, and the biochemistry and molecular biology of alloantigens and leukocyte differentiation. Manuscripts on molecules expressed on lymphoid cells, myeloid cells, platelets, and non-lineage-restricted antigens are welcomed. Lastly, the journal focuses on the immunogenetics of histocompatibility antigens in both humans and experimental animals, including their tissue distribution, regulation, and expression in normal and malignant cells, as well as the use of antigens as markers for disease.
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