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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02064

Germline-encoded TCR-MHC contacts promote TCR V gene bias in umbilical cord blood T cell repertoire

Kai Gao1, 2, 3,  Lingyan Chen2,  Yuanwei Zhang2, Yi Zhao2, 4, Ziyun Wan2,  Jinghua Wu2,  Liya Lin2, Yashu Kuang3, 5,  Jinhua Lu3, 5, Xiuqing Zhang1, 2,  Lei Tian2*,  Xiao Liu1, 2* and  Xiu Qiu3, 5, 6*
  • 1School of Future Technology, University of Chinese Academy of Sciences, China
  • 2Beijing Genomics Institute (BGI), China
  • 3Guangzhou Women and Children's Medical Center, China
  • 4School of Biology and Biological Engineering, South China University of Technology, China
  • 5Guangzhou Women and Children's Medical Center, China
  • 6Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, China

T cells recognize antigens as peptides bound to major histocompatibility complex (MHC) proteins through T cell receptors (TCRs) on their surface. To recognize a wide range of pathogens, each individual possesses a substantial number of TCRs with an extremely high degree of variability. It remains controversial whether germline-encoded TCR repertoire is shaped by MHC polymorphism and, if so, what is the preference between MHC genetic variants and TCR V gene compatibility. To investigate the “net” genetic association between MHC variations and TRBV genes, we applied quantitative trait locus (QTL) mapping to test the associations between MHC polymorphism and TCR β chain V (TRBV) genes usage using umbilical cord blood (UCB) samples of 201 Chinese newborns. We found TRBV gene and MHC loci that are predisposed to interact with one another differ from previous conclusions. The majority of MHC amino acid residues associated with the TRBV gene usage show spatial proximities in known structures of TCR-pMHC complexes. These results show for the first time that MHC variants bias TRBV gene usage in UCB of Chinese ancestry and indicate that germline-encoded contacts influence TCR-MHC interactions in intact T cell repertoires.

Keywords: TRBV gene usage, MHC genetic variations, quantitative trait locus mapping, Umbilical Cord Blood (UCB), TCR-MHC co-evolution

Received: 20 May 2019; Accepted: 15 Aug 2019.

Copyright: © 2019 Gao, Chen, Zhang, Zhao, Wan, Wu, Lin, Kuang, Lu, Zhang, Tian, Liu and Qiu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Lei Tian, Beijing Genomics Institute (BGI), Shenzhen, 518083, Guangdong Province, China,
Mx. Xiao Liu, School of Future Technology, University of Chinese Academy of Sciences, Beijing, 100049, Beijing, China,
Mx. Xiu Qiu, Guangzhou Women and Children's Medical Center, Guangzhou, China,