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Nat Biotechnol. 2014 Jul;32(7):684-92. doi: 10.1038/nbt.2938. Epub 2014 Jun 22.

Linking T-cell receptor sequence to functional phenotype at the single-cell level.

Author information

1
1] Department of Medicine, Division of Gastroenterology, Stanford University School of Medicine, Stanford, California, USA. [2] Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
2
Program in Computational and Systems Immunology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA.
3
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
4
1] Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA. [2] Program in Computational and Systems Immunology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA. [3] Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA.

Abstract

Although each T lymphocyte expresses a T-cell receptor (TCR) that recognizes cognate antigen and controls T-cell activation, different T cells bearing the same TCR can be functionally distinct. Each TCR is a heterodimer, and both α- and β-chains contribute to determining TCR antigen specificity. Here we present a methodology enabling integration of information about TCR specificity with information about T cell function. This method involves sequencing of TCRα and TCRβ genes, and amplifying functional genes characteristic of different T cell subsets, in single T cells. Because this approach retains information about individual TCRα-TCRβ pairs, TCRs of interest can be expressed and used in functional studies, for antigen discovery, or in therapeutic applications. We apply this approach to study the clonal ancestry and differentiation of T lymphocytes infiltrating a human colorectal carcinoma.

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PMID:
24952902
PMCID:
PMC4337815
DOI:
10.1038/nbt.2938
[Indexed for MEDLINE]
Free PMC Article

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