Dissection of the Human T-Cell Receptor γ Gene Repertoire in the Brain and Peripheral Blood Identifies Age- and Alzheimer's Disease-Associated Clonotype Profiles

Maria Aliseychik; Maria Aliseychik; Maria Aliseychik; Anton Patrikeev; Fedor Gusev; Anastasia Grigorenko; Anastasia Grigorenko; Tatiana Andreeva; Tatiana Andreeva; Arya Biragyn; Evgeny Rogaev; Evgeny Rogaev; Evgeny Rogaev

doi:10.3389/fimmu.2020.00012

Frontiers in Immunology (Jan 2020)

Dissection of the Human T-Cell Receptor γ Gene Repertoire in the Brain and Peripheral Blood Identifies Age- and Alzheimer's Disease-Associated Clonotype Profiles

Maria Aliseychik,
Maria Aliseychik,
Maria Aliseychik,
Anton Patrikeev,
Fedor Gusev,
Anastasia Grigorenko,
Anastasia Grigorenko,
Tatiana Andreeva,
Tatiana Andreeva,
Arya Biragyn,
Evgeny Rogaev,
Evgeny Rogaev,
Evgeny Rogaev

Affiliations

Maria Aliseychik: Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, United States
Maria Aliseychik: Department of Human Genetics and Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
Maria Aliseychik: Center for Genetics and Genetic Technologies, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
Anton Patrikeev: Department of Human Genetics and Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
Fedor Gusev: Department of Human Genetics and Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
Anastasia Grigorenko: Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, United States
Anastasia Grigorenko: Department of Human Genetics and Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
Tatiana Andreeva: Department of Human Genetics and Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
Tatiana Andreeva: Center for Genetics and Genetic Technologies, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
Arya Biragyn: Immunoregulation Section, National Institute on Aging, Baltimore, MD, United States
Evgeny Rogaev: Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, United States
Evgeny Rogaev: Department of Human Genetics and Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
Evgeny Rogaev: Center for Genetics and Genetic Technologies, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia

DOI: https://doi.org/10.3389/fimmu.2020.00012
Journal volume & issue: Vol. 11

Abstract

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The immune system contributes to neurodegenerative pathologies. However, the roles of γδ T cells in Alzheimer's disease (AD) are poorly understood. Here, we evaluated somatic variability of T-cell receptor γ genes (TRGs) in patients with AD. We performed deep sequencing of the CDR3 region of TRGs in patients with AD and control patients without dementia. TRG clones were clearly detectable in peripheral blood (PB) and non-neuronal cell populations in human brains. TRG repertoire diversity was reduced during aging. Compared with the PB, the brain showed reduced TRGV9 clonotypes but was enriched in TRGV2/4/8 clonotypes. AD-associated TRG profiles were found in both the PB and brain. Moreover, some groups of clonotypes were more specific for the brain or blood in patients with AD compared to those in controls. Our pilot deep analysis of T-cell receptor diversities in AD revealed putative brain and AD-associated immunogenic markers.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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