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亲和力成熟的HLA II类二聚体可识别抗原特异性CD4+T细胞
作者:小柯机器人 发布时间:2021/3/2 16:42:26

加拿大多伦多大学Naoto Hirano研究团队发现,亲和力成熟的HLA II类二聚体可识别抗原特异性CD4+T细胞。2021年3月1日,国际知名学术期刊《自然—生物技术》在线发表了这一成果。

研究人员表示,肽-主要组织相容性复合物(pMHC)多聚体可在从疫苗功效到癌症免疫疗法的研究中检测抗原特异性T细胞。但是,该技术应用于pMHC II类来检测CD4+T细胞时并不可靠。

通过结合分子生物学和免疫学技术,研究人员克隆了编码人白细胞抗原(HLA)-DP、HLA-DQ和HLA-DR分子的序列,这些分子具有增强的CD4结合亲和力(Kd为8.9±1.1 µM),并能够产生亲和力成熟的II类二聚体,这在体外和离体分析中均比常规多聚体更好地染色抗原特异性T细胞。

通过使用全面的二聚体库HLA-DP4(这是许多祖先族中最常见的HLA等位基因),研究人员绘制了103个HLA-DP4限制性表位,这些表位衍生自多种肿瘤相关抗原,并克隆了来自体外刺激的CD4+T细胞的同源T细胞抗原受体(TCR)基因。HLA-DP、HLA-DQ和HLA-DR等位基因中亲和力成熟的II类二聚体的可用性将有助于研究人类CD4+T细胞反应。 

附:英文原文

Title: Affinity-matured HLA class II dimers for robust staining of antigen-specific CD4 + T cells

Author: Kenji Sugata, Yukiko Matsunaga, Yuki Yamashita, Munehide Nakatsugawa, Tingxi Guo, Levon Halabelian, Yota Ohashi, Kayoko Saso, Muhammed A. Rahman, Mark Anczurowski, Chung-Hsi Wang, Kenji Murata, Hiroshi Saijo, Yuki Kagoya, Dalam Ly, Brian D. Burt, Marcus O. Butler, Tak W. Mak, Naoto Hirano

Issue&Volume: 2021-03-01

Abstract: Peptide–major histocompatibility complex (pMHC) multimers enable the detection of antigen-specific T cells in studies ranging from vaccine efficacy to cancer immunotherapy. However, this technology is unreliable when applied to pMHC class II for the detection of CD4+ T cells. Here, using a combination of molecular biological and immunological techniques, we cloned sequences encoding human leukocyte antigen (HLA)-DP, HLA-DQ and HLA-DR molecules with enhanced CD4 binding affinity (with a Kd of 8.9±1.1μM between CD4 and affinity-matured HLA-DP4) and produced affinity-matured class II dimers that stain antigen-specific T cells better than conventional multimers in both in vitro and ex vivo analyses. Using a comprehensive library of dimers for HLA-DP4, which is the most frequent HLA allele in many ancestry groups, we mapped 103 HLA-DP4-restricted epitopes derived from diverse tumor-associated antigens and cloned the cognate T-cell antigen receptor (TCR) genes from in vitro-stimulated CD4+ T cells. The availability of affinity-matured class II dimers across HLA-DP, HLA-DQ and HLA-DR alleles will aid in the investigation of human CD4+ T-cell responses.

DOI: 10.1038/s41587-021-00836-4

Source: https://www.nature.com/articles/s41587-021-00836-4

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex