Detecting T cell receptors involved in immune responses from single repertoire snapshots

Hypervariable T cell receptors (TCRs) play a key role in adaptive immunity, recognizing a vast diversity of pathogen-derived antigens. Our ability to extract clinically relevant information from large high-throughput sequencing of TCR repertoires (RepSeq) data is limited, because little is known abo...

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Vydané v:	PLoS biology Ročník 17; číslo 6; s. e3000314
Hlavní autori:	Pogorelyy, Mikhail V., Minervina, Anastasia A., Shugay, Mikhail, Chudakov, Dmitriy M., Lebedev, Yuri B., Mora, Thierry, Walczak, Aleksandra M.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 13.06.2019 Public Library of Science (PLoS)
Predmet:	Adaptive immunity Adaptive Immunity - genetics Adaptive immunology Amino acids Ankylosing spondylitis Antigen receptors, T cell Antigens Antigens, Viral Arthritis Autoimmune diseases Biology and Life Sciences Cancer immunotherapy Cluster Analysis Clustering Complementarity Determining Regions - genetics Complementarity Determining Regions - physiology Data collection Disease control Funding High-Throughput Nucleotide Sequencing - methods Humans Immune response Immunity Immunology Immunotherapy Information processing Life Sciences Lymphocytes Lymphocytes T Medical research Medicine and Health Sciences Next-generation sequencing Observations Physiological aspects Receptors Receptors, Antigen, T-Cell - immunology Receptors, Antigen, T-Cell - metabolism Receptors, Antigen, T-Cell - physiology Research and Analysis Methods Sequence Analysis, DNA - methods Software Spondylitis Supervision T cell receptors T cells T-cell receptor Vaccines Vector-borne diseases Yellow fever United States Czech Republic France United States > US Russia Immune response Lymphocytes Protein sequencing T cell receptors Nucleotide sequencing Cancer immunotherapy Sequence motif analysis Vaccination and immunization
ISSN:	1545-7885, 1544-9173, 1545-7885
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Popis
Shrnutí:	Hypervariable T cell receptors (TCRs) play a key role in adaptive immunity, recognizing a vast diversity of pathogen-derived antigens. Our ability to extract clinically relevant information from large high-throughput sequencing of TCR repertoires (RepSeq) data is limited, because little is known about TCR-disease associations. We present Antigen-specific Lymphocyte Identification by Clustering of Expanded sequences (ALICE), a statistical approach that identifies TCR sequences actively involved in current immune responses from a single RepSeq sample and apply it to repertoires of patients with a variety of disorders - patients with autoimmune disease (ankylosing spondylitis [AS]), under cancer immunotherapy, or subject to an acute infection (live yellow fever [YF] vaccine). We validate the method with independent assays. ALICE requires no longitudinal data collection nor large cohorts, and it is directly applicable to most RepSeq datasets. Its results facilitate the identification of TCR variants associated with diseases and conditions, which can be used for diagnostics and rational vaccine design.
Bibliografia:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1545-7885 1544-9173 1545-7885
DOI:	10.1371/journal.pbio.3000314