T细胞特异性的全局分析能够用于抗原发现

作者：杨超月

本期文章：《免疫》：Volume 54 Issue 3

美国斯坦福大学Mark M. Davis研究团队发现，人类非小细胞肺癌中共有T细胞特异性的全局分析可实现HLA推测和抗原发现。2021年3月9日，国际知名学术期刊《免疫》发表了这一成果。

为了鉴定具有共享抗原特异性的疾病相关T细胞受体（TCR），研究人员使用GLIPH2（grouping of lymphocyte interactions with paratope hotspots 2）算法分析了178名非小细胞肺癌患者的778,938个TCRβ链序列。研究人员确定了超过66,000个共有特异性组，其中435个与相邻肺相比在克隆中扩展并富集了肿瘤。使用酵母多肽-HLA A*02:01展示文库，研究人员鉴定了一组富集肿瘤特异性的抗原表位。这其中包括一条来自上皮蛋白TMEM161A的多肽，这个多肽在肿瘤中过表达并且是爱泼斯坦-巴尔病毒和大肠杆菌的交叉反应性抗原决定簇。

这些发现表明，这种交叉反应可能是肿瘤浸润中病毒特异性T细胞存在的基础，而病原体交叉反应可能是多种癌症的特征。这项工作中产生的方法和分析流程，以及此处定义的特异性组别，为理解癌症中的T细胞反应提供了一种资源。

附：英文原文

Title: Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery

Author: Shin-Heng Chiou, Diane Tseng, Alexandre Reuben, Vamsee Mallajosyula, Irene S. Molina, Stephanie Conley, Julie Wilhelmy, Alana M. McSween, Xinbo Yang, Daisuke Nishimiya, Rahul Sinha, Barzin Y. Nabet, Chunlin Wang, Joseph B. Shrager, Mark F. Berry, Leah Backhus, Natalie S. Lui, Heather A. Wakelee, Joel W. Neal, Sukhmani K. Padda, Gerald J. Berry, Alberto Delaidelli, Poul H. Sorensen, Elena Sotillo, Patrick Tran, Jalen A. Benson, Rebecca Richards, Louai Labanieh, Dorota D. Klysz, David M. Louis, Steven A. Feldman, Maximilian Diehn, Irving L. Weissman, Jianjun Zhang, Ignacio I. Wistuba, P. Andrew Futreal, John V. Heymach, K. Christopher Garcia, Crystal L. Mackall, Mark M. Davis

Issue&Volume: 2021/03/09

Abstract: To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity,we analyzed 778,938 TCRβ chain sequences from 178 non-small cell lung cancer patientsusing the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm.We identified over 66,000 shared specificity groups, of which 435 were clonally expandedand enriched in tumors compared to adjacent lung. The antigenic epitopes of one suchtumor-enriched specificity group were identified using a yeast peptide-HLA A02:01 display library. These included a peptide from the epithelial protein TMEM161A,which is overexpressed in tumors and cross-reactive epitopes from Epstein-Barr virusand E. coli. Our findings suggest that this cross-reactivity may underlie the presence of virus-specificT cells in tumor infiltrates and that pathogen cross-reactivity may be a feature ofmultiple cancers. The approach and analytical pipelines generated in this work, aswell as the specificity groups defined here, present a resource for understandingthe T cell response in cancer.

DOI: 10.1016/j.immuni.2021.02.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00080-7

期刊信息

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