Characterisation of the HLA-DQ alpha eplet 52SK targeting the DQA1*01 alleles family

IF 5.9 4区 医学 Q2 CELL BIOLOGY HLA Pub Date : 2024-10-01 DOI:10.1111/tan.15700
Magali Devriese, Jar How Lee, Tina Meng, Thoa Nong, Neng Jen Remi Shih, François A. Lemonnier, Hiroko Miyadera, Lisa Giraldo, Cédric Usureau, Olivier Toutirais, Dave Lowe, Jean Luc Taupin
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Abstract

Eplet 52SK is unique in the HLA eplet registry as targeting the whole family of DQA1*01 alleles. It is proposed as an antibody-verified eplet but has not been validated enough to deserve this label. Especially, confusion can occur with reactivity targeting the 52PQ eplet which is present on the DQB1*05 and DQB1*06 alleles families, as DQ molecule stability imposes DQA1*01 to selectively associate with these DQ-β families only. Using two Luminex single antigen (LSA) assays from two vendors, beads bearing DR-α/DQ6 heterodimers, a special build LSA panel of additional DQ beads, and an adsorption/elution strategy relying on cells from deceased donors or recombinant cells solely expressing one DQ antigen, we definitely established the antibody-verified status of eplet 52SK using patients' sera reacting only against the DQ5 and DQ6 beads of the One Lambda LSA panel in routine patients' follow up. We also show that reactivity against this eplet is not a rare event among anti-DQ1 immunisation. This study further strengthens the importance of considering the DQA1 locus in immunological studies of HLA and in organ allocation strategies.

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以 DQA1*01 等位基因家族为目标的 HLA-DQ alpha eplet 52SK 的特征。
外显子 52SK 在 HLA 外显子登记册中是独一无二的,因为它针对的是整个 DQA1*01 等位基因家族。它被建议作为抗体验证的外显子,但尚未得到足够的验证,因此不值得贴此标签。特别是,由于 DQ 分子的稳定性要求 DQA1*01 只能选择性地与这些 DQ-β 家族结合,因此针对 52PQ 表位的反应性可能会与 DQB1*05 和 DQB1*06 等位基因家族混淆。通过使用两个供应商提供的两种 Luminex 单抗原(LSA)检测方法、带有 DR-α/DQ6 异源二聚体的珠子、由其他 DQ 珠子组成的特殊 LSA 面板,以及依赖于死亡供体细胞或仅表达一种 DQ 抗原的重组细胞的吸附/洗脱策略,我们在常规患者随访中使用仅对 One Lambda LSA 面板中的 DQ5 和 DQ6 珠子产生反应的患者血清,确定了 eplet 52SK 的抗体验证状态。我们还发现,在抗 DQ1 免疫接种中,对该表位的反应并不罕见。这项研究进一步加强了在 HLA 免疫学研究和器官分配策略中考虑 DQA1 位点的重要性。
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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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