Monitoring the T-cell receptor repertoire at single-clone resolution.
The adaptive immune system recognizes billions of unique antigens using highly variable T-cell receptors. The alphabeta T-cell receptor repertoire includes an estimated 10(6) different rearranged beta chains per individual. This paper describes a novel micro-array based method that monitors the beta chain repertoire with a resolution of a single T-cell clone. These T-arrays are quantitative and detect T-cell clones at a frequency of less than one T cell in a million, which is 2 logs more sensitive than spectratyping (immunoscope), the current standard in repertoire analysis. Using T-arrays we detected CMV-specific CD4+ and CD8+ T-cell clones that expanded early after viral antigen stimulation in vitro and in vivo. This approach will be useful in monitoring individual T-cell clones in diverse experimental settings, and in identification of T-cell clones associated with infectious disease, autoimmune disease and cancer.
Bonarius
Hendrik P J
HP
Division of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Netherlands.
Baas
Frank
F
Remmerswaal
Ester B M
EB
van Lier
René A W
RA
ten Berge
Ineke J M
IJ
Tak
Paul P
PP
de Vries
Niek
N
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics; D001483:Base Sequence; D002999:Clone Cells; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA