An Epstein-Barr virus-associated superantigen.
More than 90% of adults are latently infected with Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, a self-limiting lymphoproliferative disease characterized by extensive T cell activation. Reactivation of this herpesvirus during immunosuppression is often associated with oncogenesis. These considerations led us to analyze the early events that occur after exposure of the immune system to EBV. Strong major histocompatibility complex (MHC) class II-dependent but not MHC-restricted, T cell proliferation was observed in vitro in response to autologous, lytically infected EBV-transformed B cells. By measuring the appearance of the early activation marker CD69 on individual T cell V beta subsets, we could demonstrate selective activation of human V beta 13- T cells. This was confirmed with murine T cell hybridomas expressing various human BV genes. While EBV- Burkitt's lymphoma cells were nonstimulatory, they induced V beta-restricted T cell activation after EBV infection. EBV specific activation was also demonstrated in cord blood cells, excluding a recall-antigen response. Thus, all of the characteristics of a superantigen-stimulated response are seen, indicating that induction of the EBV lytic cycle is associated with the expression of a superantigen in B cells. A model is presented proposing a role for the superantigen in infection, latency, and oncogenesis.
Sutkowski
N
N
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Palkama
T
T
Ciurli
C
C
Sekaly
R P
RP
Thorley-Lawson
D A
DA
Huber
B T
BT
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D002472:Cell Transformation, Viral; D006684:HLA-DR Antigens / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000737:chemistry; D007244:Infectious Mononucleosis / Q000276:immunology*; D037181:Lectins, C-Type; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D018089:Superantigens / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D018089:Superantigens; D000099192:CD69 Antigens