The same TCR (N)Dbeta(N)Jbeta junctional region is associated with several different vbeta13 subtypes in a multiple sclerosis patient at the onset of the disease.
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 Vbeta13 cell clones in cerebrospinal fluid (CSF) and in peripheral blood lymphocytes (PBLs). Sequencing of the beta13(+) chains of T cells recovered from the CSF revealed high interindividual diversity, and no particular Vbeta13(+) rearrangements were shown to be myelin-autoreactive. Within the overall Vbeta13 repertoire in the CSF of patient MS3 at the onset of the disease, most of the overrepresented (N)Dbeta(N)Jbeta junctional regions were found to be associated with two or three different Vbeta13 segments. These rearrangements were most common in the PBLs of patient MS3. No such associations were detected in the Vbeta5 multigene family that was used as a control. Thus, Vbeta13 T cells infiltrating the CSF from patient MS3 may have been selected on the basis of both the Vbeta13 segments and the (N)Dbeta(N)Jbeta junctional CDR3 sequence.
Démoulins
Thomas
T
CEA, Service de Neurovirologie, CRSSA, EPHE, Université Paris XI, Fontenay-aux-Roses, France.
Mouthon
Franck
F
Clayette
Pascal
P
Bequet
Daniel
D
Gachelin
Gabriel
G
Dormont
Dominique
D
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D022801:Complementarity Determining Regions / Q000276:immunology; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell