Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis
| Autor: | Paolo Somma, Maria Teresa Fiorillo, Stefania Cannoni, Adamo Diamantini, Giovanni Ristori, Giovanna Borsellino, Rosa Sorrentino, Luca Battistini, Marco Salvetti |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Multiple Sclerosis T cell Receptors Antigen T-Cell alpha-beta Immunology Amino Acid Motifs Molecular Sequence Data Biology CD8-Positive T-Lymphocytes medicine.disease_cause Polymerase Chain Reaction Autoimmunity Antigen T-Lymphocyte Subsets medicine Immunology and Allergy Cytotoxic T cell Humans Amino Acid Sequence Genetics Multiple sclerosis Repertoire T-cell receptor Cell Biology Sequence Analysis DNA Twins Monozygotic Middle Aged medicine.disease Complementarity Determining Regions medicine.anatomical_structure Female CD8 |
| Zdroj: | Journal of leukocyte biology. 81(3) |
| ISSN: | 0741-5400 |
| Popis: | 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 β-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. |
| Databáze: | OpenAIRE |
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