Expansion of a recurrent V beta 5.3+ T-cell population in newly diagnosed and untreated HLA-DR2 multiple sclerosis patients.
We have used a PCR-based technology to study the V beta 5 and V beta 17 repertoire of T-cell populations in HLA-DR2 multiple sclerosis (MS) patients. We have found that the five MS DR2 patients studied present, at the moment of diagnosis and prior to any treatment, a marked expansion of a CD4+ T-cell population bearing V beta 5-J beta 1.4 beta chains. The sequences of the complementarity-determining region 3 of the expanded T cells are highly homologous. One shares structural features with that of the T cells infiltrating the central nervous system and of myelin basic protein-reactive T cells found in HLA-DR2 MS patients. An homologous sequence was not detectable in MS patients expressing DR alleles other than DR2. However, it is detectable but not expanded in healthy DR2 individuals. The possible mechanisms leading to its in vivo proliferation at the onset of MS are discussed.
Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale U277, Institut Pasteur, Paris, France.
P
P
Musette
D
D
Bequet
C
C
Delarbre
G
G
Gachelin
P
P
Kourilsky
D
D
Dormont
D001483:Base Sequence; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D015802:HLA-DR2 Antigen / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry*
D015802:HLA-DR2 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta