Major histocompatibility complex and peptide specificity underpin CD8+ T cell direct alloresponse.

IF 8.9 2区 医学 Q1 SURGERY American Journal of Transplantation Pub Date : 2024-10-20 DOI:10.1016/j.ajt.2024.10.011
Weiwen Zhang, Fernanda M Roversi, Anna B Morris, Kristina Ortiz, Grace Zhou, Annette Hadley, Xueqiong Zhang, Juliete A F Silva, Cynthia P Breeden, Zhuldyz Zhanzak, Haydn T Kissick, Christian P Larsen
{"title":"Major histocompatibility complex and peptide specificity underpin CD8<sup>+</sup> T cell direct alloresponse.","authors":"Weiwen Zhang, Fernanda M Roversi, Anna B Morris, Kristina Ortiz, Grace Zhou, Annette Hadley, Xueqiong Zhang, Juliete A F Silva, Cynthia P Breeden, Zhuldyz Zhanzak, Haydn T Kissick, Christian P Larsen","doi":"10.1016/j.ajt.2024.10.011","DOIUrl":null,"url":null,"abstract":"<p><p>The direct alloresponse, pivotal in transplant rejection, occurs when recipient T cells recognize intact allogeneic peptide-major histocompatibility complex (pMHC) complexes. Despite extensive research, our understanding of alloreactive CD8<sup>+</sup> T cells against an individual MHC allele in humans remains limited, especially their precursor frequency, MHC specificity, and peptide specificity. By using K562 cell-based artificial antigen-presenting cells expressing human leukocyte antigen (HLA)-A∗01:01, HLA-A∗02:01, or HLA-A∗03:01, we determined that the precursor frequency of alloreactive CD8<sup>+</sup> T cells against a single MHC allele ranges from 0.1% to 0.5%. Further, these cells exhibited MHC specificity regarding proliferation, activation, interferon gamma secretion, and cytolytic ability, with limited crossreactivity toward nontargeted MHC alleles. Focusing on anti-A2 alloreactive CD8<sup>+</sup> T cells, we developed a peptide-exchangeable artificial antigen-presenting cell that displays selected peptides on HLA-A∗02:01. From a set of 95 computationally curated A2-restricted peptides most abundant in renal tubular cells, we identified 2 immunogenic kidney peptides across multiple donors. Overall, our findings significantly enhance the understanding of direct alloresponse and provide a toolkit for future mechanistic studies and reproducible patient monitoring.</p>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.9000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajt.2024.10.011","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0

Abstract

The direct alloresponse, pivotal in transplant rejection, occurs when recipient T cells recognize intact allogeneic peptide-major histocompatibility complex (pMHC) complexes. Despite extensive research, our understanding of alloreactive CD8+ T cells against an individual MHC allele in humans remains limited, especially their precursor frequency, MHC specificity, and peptide specificity. By using K562 cell-based artificial antigen-presenting cells expressing human leukocyte antigen (HLA)-A∗01:01, HLA-A∗02:01, or HLA-A∗03:01, we determined that the precursor frequency of alloreactive CD8+ T cells against a single MHC allele ranges from 0.1% to 0.5%. Further, these cells exhibited MHC specificity regarding proliferation, activation, interferon gamma secretion, and cytolytic ability, with limited crossreactivity toward nontargeted MHC alleles. Focusing on anti-A2 alloreactive CD8+ T cells, we developed a peptide-exchangeable artificial antigen-presenting cell that displays selected peptides on HLA-A∗02:01. From a set of 95 computationally curated A2-restricted peptides most abundant in renal tubular cells, we identified 2 immunogenic kidney peptides across multiple donors. Overall, our findings significantly enhance the understanding of direct alloresponse and provide a toolkit for future mechanistic studies and reproducible patient monitoring.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
MHC 和多肽特异性是 CD8+ T 细胞直接异反应的基础。
当受体 T 细胞识别到完整的异体肽-MHC 复合物时,就会产生直接异体反应,这种反应在移植排斥中起着关键作用。尽管进行了大量研究,但我们对人类针对单个 MHC 等位基因的异源反应 CD8+ T 细胞的了解仍然有限,尤其是它们的前体频率、MHC 特异性和肽特异性。通过使用表达 HLA-A*01:01、HLA-A*02:01 或 HLA-A*03:01 的基于 K562 细胞的人工抗原递呈细胞(aAPCs),我们确定了针对单个 MHC 等位基因的异源性 CD8+ T 细胞的前体频率为 0.1% 到 0.5%。此外,这些细胞在增殖、活化、IFN-γ分泌和细胞溶解能力方面表现出MHC特异性,对非目标MHC等位基因的交叉反应有限。我们以抗 A2 特异反应的 CD8+ T 细胞为重点,开发了一种可显示 HLA-A*02:01 上选定肽的肽交换型 aAPC。我们从肾小管细胞中最丰富的一组 95 个经过计算筛选的 A2 限制肽中,在多个供体中发现了两种免疫原性肾肽。总之,我们的研究结果大大提高了人们对直接异体反应的认识,并为未来的机理研究和可重复的患者监测提供了一个工具包。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
18.70
自引率
4.50%
发文量
346
审稿时长
26 days
期刊介绍: The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide. The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.
期刊最新文献
A novel intravascular bioartificial pancreas device shows safety and islet functionality over thirty days in non-diabetic swine. Liver transplantation and bariatric surgery: is sleeve gastrectomy really the panacea? Prognostic implications of lung cancers incidentally identified on explant: A joint study of the Scientific Registry of Transplant Recipients and the National Cancer Database. Novel Modified Iliac Artery Stent Graft with Side Branch Extension Facilitating Kidney Transplant in Severe Aortoiliac Occlusive Disease. Serologic screening and molecular surveillance of Kaposi sarcoma herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) infections for early recognition and effective treatment of KSHV-associated inflammatory cytokine syndrome (KICS) in solid organ transplant recipients.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1