Myelin basic protein and myelin oligodendrocyte glycoprotein T-cell repertoire in childhood and juvenile multiple sclerosis.
Multiple sclerosis (MS) is usually a disease of young adulthood, its clinical onset occurring between 20 and 40 years of age; however, today there is general consensus that MS can also occur in children, adolescents and even in infants. In order to gain further insight into the T-cell repertoire present in this particular group of patients myelin basic protein (MBP)-, MBP exon-2- and myelin oligodendrocyte glycoprotein (MOG)Igd-specific T-cell lines (TCLs) were isolated from 18 patients whose symptoms had started before the age of 16. Epitope specificity was established by measuring proliferative responses, and interferon-y (IFN-y) secretion by using a panel of overlapping synthetic peptides. For MOGIgd, the T-cell response was focused on three main immunodominant epitopes comprising residues 1-26, 36-60 and 63-87. For MBP the predominant immune responses were directed against peptides 83-102, 139-153 and 146-162. When compared to those observed in adult-onset MS patients, anti-MOGIgd specificity and anti-MBP responses showed similar results. Moreover, the number of MBP exon-2 TCLs isolated, and the magnitude of the specific IFN-gamma secretion induced were similar, both in childhood/juvenile-onset and adult-onset MS patients. Thus, despite differences in the clinical and neuroimaging manifestations of MS, these results would seem to indicate that both the spectrum of MBP found, as well as the MOGIgd epitopes recognized by peripheral blood T cells in MS, appear to be similar for childhood/juvenile-onset and adult-onset patients.
Correale
Jorge
J
Department of Neurology, Raúl Carrea Institute for Neurological Research, (FLENI), Montañeses 2325 (1428), Buenos Aires, Argentina. jcorreale@fleni.org.ar
Tenembaum
Silvia N
SN
D000293:Adolescent; D017668:Age of Onset; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D007371:Interferon-gamma