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胚系编码的 TCR-MHC 接触促进脐带血 T 细胞受体库中 TCR V 基因偏倚。

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

机构信息

BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.

BGI-Shenzhen, Shenzhen, China.

出版信息

Front Immunol. 2019 Aug 30;10:2064. doi: 10.3389/fimmu.2019.02064. eCollection 2019.

DOI:10.3389/fimmu.2019.02064
PMID:31543879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6730489/
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.

摘要

T 细胞通过其表面的 T 细胞受体 (TCR) 识别与主要组织相容性复合体 (MHC) 蛋白结合的抗原作为肽。为了识别广泛的病原体，每个人都拥有大量具有极高变异性的 TCR。MHC 多态性是否塑造了胚系编码的 TCR 库，以及如果是这样，MHC 遗传变异体和 TCR V 基因兼容性之间的偏好是什么，这仍然存在争议。为了研究 MHC 变异与 TRBV 基因之间的“净”遗传关联，我们应用数量性状基因座 (QTL) 作图来测试脐带血 (UCB) 样本中 201 名中国新生儿的 MHC 多态性与 TCRβ链 V(TRBV)基因使用之间的关联。我们发现与 TRBV 基因使用相互作用的倾向的 TRBV 基因和 MHC 基因座与之前的结论不同。与 TRBV 基因使用相关的大多数 MHC 氨基酸残基在 TCR-pMHC 复合物的已知结构中具有空间接近性。这些结果首次表明 MHC 变体偏向中国血统 UCB 中的 TRBV 基因使用，并表明胚系编码的接触影响完整 T 细胞库中的 TCR-MHC 相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/c3f961e03b52/fimmu-10-02064-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/fe3b9d42e264/fimmu-10-02064-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/a3048a41b4fa/fimmu-10-02064-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/ef255a4564bc/fimmu-10-02064-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/c3f961e03b52/fimmu-10-02064-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/fe3b9d42e264/fimmu-10-02064-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/a3048a41b4fa/fimmu-10-02064-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/ef255a4564bc/fimmu-10-02064-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8aa/6730489/c3f961e03b52/fimmu-10-02064-g0004.jpg

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