Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis.
Autoreactive CD4+ and CD8+ T cells directed against CNS autoantigens may play a role in the development of multiple sclerosis (MS). Identical twins share the same genetic background but not the TCR repertoire that is shaped by the encounter with self or foreign antigens. To gain insights into the interplay between MS and T cell repertoire, peripheral blood CD4+ and CD8+ T lymphocytes and their CCR7+/CCR7- subsets from five pairs of identical twins (four discordant and one concordant for MS; none of which had taken disease-modifying therapy) were compared by TCR beta-chain (TCRB) complementary-determining region 3 (CDR3) spectratyping. CD4+ T cells generally showed a Gaussian distribution, whereas CD8+ T cells exhibited subject-specific, widely skewed TCR spectratypes. There was no correlation between CD8+ T cell oligoclonality and disease. Sequencing of predominant spectratype expansions revealed shared TCRB-CDR3 motifs when comparing inter- and/or intrapair twin members. In many cases, these sequences were homologous to published TCRs, specific for viruses implicated in MS pathogenesis, CNS autoantigens, or copaxone [glatiramer acetate (GA)], implying the occurrence of naturally GA-responding CD8+ T cells. It is notable that these expanded T cell clones with putative pathogenic or regulatory properties were present in the affected as well as in the healthy subject, thus suggesting the existence of a "MS predisposing trait" shared by co-twins discordant for MS.
Somma
Paolo
P
Department of Cell Biology and Development, University of Rome La Sapienza, Via dei Sardi 70, 00185 Rome, Italy.
Ristori
Giovanni
G
Battistini
Luca
L
Cannoni
Stefania
S
Borsellino
Giovanna
G
Diamantini
Adamo
A
Salvetti
Marco
M
Sorrentino
Rosa
R
Fiorillo
Maria Teresa
MT
D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000145:classification* / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000032:analysis / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA / Q000379:methods; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014430:Twins, Monozygotic
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta