The same TCR (N)Dβ(N)Jβ junctional region is associated with several different vβ13 subtypes in a multiple sclerosis patient at the onset of the disease

Abstract

In multiple sclerosis (MS), the T-cell receptors (TCRS) of autoreactive T lymphocytes recognize various myelin components or derivatives including peptides of the myelin basic protein (MBP). Using the exhaustive immunoscope approach we showed that the T-cell repertoires of MS patients differ from those of healthy controls, with expansion of Vβ13 cell clones in cerebrospinal fluid (CSF) and in peripheral blood lymphocytes (PBLs). Sequencing of the β13+ chains of T cells recovered from the CSF revealed high interindividual diversity, and no particular Vβ13+ rearrangements were shown to be myelin-autoreactive. Within the overall Vβ13 repertoire in the CSF of patient MS3 at the onset of the disease, most of the overrepresented (N)Dβ(N)Jβ junctional regions were found to be associated with two or three different Vβ13 segments. These rearrangements were most common in the PBLs of patient MS3. No such associations were detected in the Vβ5 multigene family that was used as a control. Thus, Vβ13 T cells infiltrating the CSF from patient MS3 may have been selected on the basis of both the Vβ13 segments and the (N)Dβ(N)Jβ junctional CDR3 sequence.

Keywords

• Multiple sclerosis
• Autoimmunity
• Neuroimmunology
• Myelin basic protein
• T-cell receptors
• CDR3