title: Mother and child T cell receptor repertoires: deep profiling study.
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.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Putintseva
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Britanova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Dmitriy B
authors.initials: DB
authors.lastname: Staroverov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Ekaterina M
authors.initials: EM
authors.lastname: Merzlyak
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Turchaninova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shugay
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Dmitriy A
authors.initials: DA
authors.lastname: Bolotin
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pogorelyy
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Ilgar Z
authors.initials: IZ
authors.lastname: Mamedov
authors.affiliation: Federal Scientific Clinical Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Bobrynina
authors.affiliation: Federal Scientific Clinical Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Maschan
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia.
authors.forename: Yuri B
authors.initials: YB
authors.lastname: Lebedev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , Moscow , Russia ; Central European Institute of Technology (CEITEC), Masaryk University , Brno , Czech Republic.
authors.forename: Dmitriy M
authors.initials: DM
authors.lastname: Chudakov
keywords: NGS; T cell receptor; TCR repertoires; autoimmune diseases; haploidentical transplantation; maternal-fetal exchange; microchimerism; public clonotypes