Demoulins T, Naccache L, Clayette P, Musette P, Bequet D, Gachelin G, Dormont D.
Service de Neurovirologie, CEA, CRSSA, EPHE, Institut Pasteur, Paris, France.
Anti-myelin basic protein (MBP) autoreactive T cells play a key role in the pathogenesis of multiple sclerosis.
Thus, we applied the Immunoscope strategy to cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBLs) of an HLA-DR2 patient.
Both compartments showed major expansion for the Vbeta13S5 chain, which was associated in peripheral blood with significant proliferation of PBLs in response to MBP and the 84-102 HLA-DR2-restricted peptide.
Sequencing revealed a unique nucleotide sequence in the CSF that gives rise to the amino acid sequence Vbeta13S5-RPGQGDQETQ-Jbeta2.5 if translated.
This CDR3 sequence had already been reported to be reactive against the 84-102 peptide.
This specific sequence was not detected in PBLs on day 0, whereas it was readily detectable on day 6 culture samples.
Thus, cell culture may lead to enrichment in a T cell clone identified as autoreactive.