High-resolution analysis of the human T-cell receptor repertoire.
Unbiased dissection of T-cell receptor (TCR) repertoire diversity at the nucleotide level could provide important insights into human immunity. Here we show that TCR ligation-anchored-magnetically captured PCR (TCR-LA-MC PCR) identifies TCR α- and β-chain diversity without sequence-associated or quantitative restrictions in healthy and diseased conditions. TCR-LA-MC PCR identifies convergent recombination events, classifies different stages of cutaneous T-cell lymphoma in vivo and demonstrates TCR reactivation after in vitro cytomegalovirus stimulation. TCR-LA-MC PCR allows ultra-deep data access to both physiological TCR diversity and mechanisms influencing clonality in all clinical settings with restricted or distorted TCR repertoires.
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Eliana
E
Ruggiero
Division of Immunogenetics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Jan P
JP
Nicolay
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Raffaele
R
Fronza
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Anne
A
Arens
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Anna
A
Paruzynski
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Ali
A
Nowrouzi
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Gökçe
G
Ürenden
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Christina
C
Lulay
Institute for Clinical Chemistry, University Medical Center, Ruprecht-Karls-University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Sven
S
Schneider
Department of Dermatology, Venereology and Allergology, University Medical Center, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Sergij
S
Goerdt
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Hanno
H
Glimm
Division of Immunogenetics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Peter H
PH
Krammer
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Manfred
M
Schmidt
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Christof
C
von Kalle
D000328:Adult; D000368:Aged; D000818:Animals; D003586:Cytomegalovirus Infections / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics*; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012751:Sezary Syndrome / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta