Multiple sclerosis retrovirus particles and recombinant envelope trigger an abnormal immune response in vitro, by inducing polyclonal Vbeta16 T-lymphocyte activation.
A retroviral element (MSRV) defining a family of genetically inherited endogenous retroviruses (HERV-W) has recently been characterized in cell cultures from patients with multiple sclerosis (MS). To address the possible relationship with MS, direct detection of circulating virion RNA was proposed but revealed technically difficult to perform in standardized conditions, in the face of multiple endogenous HERV-W copies. A parallel approach has evaluated MSRV potential pathogenicity in relation to characteristic features of multiple sclerosis, in particular, T-lymphocyte-mediated immunopathology. We report here that MSRV particles induce T-lymphocyte response with a bias in the Vbeta16 chain usage in surface receptor, whatever the HLA DR of the donor. A recombinant MSRV envelope-but not core-protein reproduced similar nonconventional activation. Molecular analysis of Vbeta CDR3 showed that Vbeta16 expansions are polyclonal. Our results thus provide evidence that MSRV envelope protein can trigger an abnormal immune response with similar characteristics to that of superantigens.
Perron
H
H
BioMérieux-Pierre Fabre, R&D, Chemin de L'Orme, Marcy L'Etoile, 69280, France. herve_perron@eu.biomerieux.com
Jouvin-Marche
E
E
Michel
M
M
Ounanian-Paraz
A
A
Camelo
S
S
Dumon
A
A
Jolivet-Reynaud
C
C
Marcel
F
F
Souillet
Y
Y
Borel
E
E
Gebuhrer
L
L
Santoro
L
L
Marcel
S
S
Seigneurin
J M
JM
Marche
P N
PN
Lafon
M
M
D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology / Q000821:virology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000276:immunology*; D014771:Virion / Q000276:immunology
D000956:Antigens, Viral; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins