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Germline-Encoded TCR-MHC Contacts Promote TCR V Gene Bias in Umbilical Cord Blood T Cell Repertoire.

Published version
Peer-reviewed

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Type

Article

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Authors

Gao, Kai 
Zhang, Yuanwei 
Zhao, Yi 
Wan, Ziyun 

Abstract

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.

Description

Keywords

MHC genetic variations, TCR-MHC co-evolution, TRBV gene usage, quantitative trait locus mapping, umbilical cord blood, Asian People, Fetal Blood, Germ Cells, Histocompatibility Antigens, Humans, Infant, Newborn, Major Histocompatibility Complex, Peptides, Receptors, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes

Journal Title

Front Immunol

Conference Name

Journal ISSN

1664-3224
1664-3224

Volume Title

10

Publisher

Frontiers Media SA