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Front Immunol. 2013 Dec 25;4:463. doi: 10.3389/fimmu.2013.00463. eCollection 2013.

Mother and child T cell receptor repertoires: deep profiling study.

Author information

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
2
Federal Scientific Clinical Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.
3
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia ; Central European Institute of Technology (CEITEC), Masaryk University , Brno , Czech Republic.

Abstract

The relationship between maternal and child immunity has been actively studied in the context of complications during pregnancy, autoimmune diseases, and haploidentical transplantation of hematopoietic stem cells and solid organs. Here, we have for the first time used high-throughput Illumina HiSeq sequencing to perform deep quantitative profiling of T cell receptor (TCR) repertoires for peripheral blood samples of three mothers and their six children. Advanced technology allowed accurate identification of 5 × 10(5) to 2 × 10(6) TCR beta clonotypes per individual. We performed comparative analysis of these TCR repertoires with the aim of revealing characteristic features that distinguish related mother-child pairs, such as relative TCR beta variable segment usage frequency and relative overlap of TCR beta complementarity-determining region 3 (CDR3) repertoires. We show that thymic selection essentially and similarly shapes the initial output of the TCR recombination machinery in both related and unrelated pairs, with minor effect from inherited differences. The achieved depth of TCR profiling also allowed us to test the hypothesis that mature T cells transferred across the placenta during pregnancy can expand and persist as functional microchimeric clones in their new host, using characteristic TCR beta CDR3 variants as clonal identifiers.

KEYWORDS:

NGS; T cell receptor; TCR repertoires; autoimmune diseases; haploidentical transplantation; maternal-fetal exchange; microchimerism; public clonotypes

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