T-cell receptor repertoire of human peripheral CD161hiTRAV1-2+ MAIT cells revealed by next generation sequencing and single cell analysis

Kathrin Held; Eduardo Beltrán; Markus Moser; Reinhard Hohlfeld; Klaus Dornmair

doi:10.1016/j.humimm.2015.09.002

T-cell receptor repertoire of human peripheral CD161hiTRAV1-2+ MAIT cells revealed by next generation sequencing and single cell analysis

Hum Immunol. 2015 Sep;76(9):607-14. doi: 10.1016/j.humimm.2015.09.002. Epub 2015 Sep 14.

Authors

Kathrin Held¹, Eduardo Beltrán², Markus Moser³, Reinhard Hohlfeld⁴, Klaus Dornmair⁴

Affiliations

¹ Institute of Clinical Neuroimmunology, Klinikum der Universität Muenchen, Munich, Germany. Electronic address: Kathrin.Held@med.uni-muenchen.de.
² Institute of Clinical Neuroimmunology, Klinikum der Universität Muenchen, Munich, Germany.
³ Department of Molecular Medicine, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
⁴ Institute of Clinical Neuroimmunology, Klinikum der Universität Muenchen, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilian-University, Munich, Germany.

PMID: 26382249
DOI: 10.1016/j.humimm.2015.09.002

Abstract

Mucosal-associated invariant T (MAIT) cells are a T-cell subset that expresses a conserved TRAV1-2 (Vα7.2) T-cell receptor (TCR) chain and the surface marker CD161. They are involved in the defence against microbes as they recognise small organic molecules of microbial origin that are presented by the non-classical MHC molecule 1 (MR1). MAIT cells express a semi-restricted TCR α chain with TRAV1-2 preferentially linked to TRAJ33, TRAJ12, or TRAJ20 which pairs with a limited set of β chains. To investigate the TCR repertoire of human CD161(hi)TRAV1-2(+) T cells in depth we analysed the α and β chains of this T-cell subset by next generation sequencing. Concomitantly we analysed 132 paired α and β chains from single cells to assess the αβ pairing preferences. We found that the CD161(hi)TRAV1-2(+) TCR repertoire in addition to the typical MAIT TCRs further contains polyclonal elements reminiscent of classical αβ T cells.

Keywords: CD161; MAIT cells; T-cell receptor; T-cell receptor repertoire.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Amino Acid Sequence
CD4-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / metabolism
Complementarity Determining Regions / chemistry
Complementarity Determining Regions / genetics
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mucous Membrane / cytology*
Mucous Membrane / immunology
NK Cell Lectin-Like Receptor Subfamily B / genetics*
NK Cell Lectin-Like Receptor Subfamily B / metabolism
Peptide Fragments / chemistry
Position-Specific Scoring Matrices
Receptors, Antigen, T-Cell, alpha-beta / chemistry
Receptors, Antigen, T-Cell, alpha-beta / genetics*
Receptors, Antigen, T-Cell, alpha-beta / metabolism
Single-Cell Analysis
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism*

Substances

Complementarity Determining Regions
NK Cell Lectin-Like Receptor Subfamily B
Peptide Fragments
Receptors, Antigen, T-Cell, alpha-beta