High-throughput pairing of T cell receptor α and β sequences.
The T cell receptor (TCR) protein is a heterodimer composed of an α chain and a β chain. TCR genes undergo somatic DNA rearrangements to generate the diversity of T cell binding specificities needed for effective immunity. Recently, high-throughput immunosequencing methods have been developed to profile the TCR α (TCRA) and TCR β (TCRB) repertoires. However, these methods cannot determine which TCRA and TCRB chains combine to form a specific TCR, which is essential for many functional and therapeutic applications. We describe and validate a method called pairSEQ, which can leverage the diversity of TCR sequences to accurately pair hundreds of thousands of TCRA and TCRB sequences in a single experiment. Our TCR pairing method uses standard laboratory consumables and equipment without the need for single-cell technologies. We show that pairSEQ can be applied to T cells from both blood and solid tissues, such as tumors.
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Bryan
B
Howie
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Anna M
AM
Sherwood
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Ashley D
AD
Berkebile
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Jan
J
Berka
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Ryan O
RO
Emerson
Adaptive Biotechnologies, Seattle, WA 98102, USA.
David W
DW
Williamson
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Ilan
I
Kirsch
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Marissa
M
Vignali
Adaptive Biotechnologies, Seattle, WA 98102, USA.
Mark J
MJ
Rieder
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Christopher S
CS
Carlson
Adaptive Biotechnologies, Seattle, WA 98102, USA. Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. hrobins@fredhutch.org.
Harlan S
HS
Robins
D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta