Longitudinal study of myelin basic protein-specific T-cell receptors during the course of multiple sclerosis.
This study analyzed the stability of the myelin basic protein (MBP)-specific T-cell receptor (TCR) repertoire during the course of multiple sclerosis (MS) in three patients who were monitored for three years by gadolinium-enhanced magnetic resonance imaging. Bulk-culture T-cell lines (TCLs) were generated from 3-4 time points for each patient, including times of active and quiescent disease. TCR analysis of these TCLs indicated that both the V alpha and V beta usage was similar over time for each patient. Sequencing of TCRs demonstrated conserved complementarity-determining region 3 (CDR3) sequences within TCLs that expressed the same V alpha segment over time, although the J alpha usage was different for each TCR. This indicates that the population of MBP-reactive T-cells is changing during the course of MS, but that host and/or environmental factors may be selecting T-cells with particular MHC/peptide binding domains.
Lovett-Racke
A E
AE
Neuroimmunology Branch, National Institute of Neurologic Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Martin
R
R
McFarland
H F
HF
Racke
M K
MK
Utz
U
U
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D000939:Epitopes; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D000939:Epitopes; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta