Human T cells respond to mouse mammary tumor virus-encoded superantigen: V beta restriction and conserved evolutionary features.
Mouse mammary tumor virus (MMTV)-encoded superantigens (SAGs) influence the murine T cell repertoire and stimulate a strong mixed lymphocyte response in vitro. These SAGs are encoded by the open reading frame of the 3' long terminal repeat of MMTV, termed MMTV SAGs. The T cell response to MMTV SAGs is V beta restricted and requires expression of the class II molecules of the major histocompatibility complex (MHC) on the presenting cells. While human T cells respond to bacterial SAGs, it is not known if human T cells or human MHC class II molecules can interact with MMTV SAGs. A fibroblastic cell line expressing the human MHC class II molecule HLA-DR1 and the Mtv-7 sag gene encoding Mls-1 was used to stimulate human T cells. We show here that human T cells efficiently proliferate in response to Mls-1 presented by HLA-DR1. This T cell response was inhibited by mAbs directed against CD4 or MHC class II molecules but not by mAbs specific for CD8 or MHC class I molecules. Moreover, the response to Mls-1 was limited to human T cells expressing a restricted set of T cell receptor V beta chains. Human T cells expressing V beta 12, 13, 14, 15, and 23 were selectively amplified after Mtv-7 sag stimulation. Interestingly, these human V beta s share the highest degree of homology with the mouse V beta s interacting with Mls-1. These results show a strong evolutionary conservation of the structures required for the presentation and the response to retrovirally encoded endogenous SAGs, raising the possibility that similar elements operate in humans to shape the T cell repertoire.
Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Canada.
N
N
Labrecque
H
H
McGrath
M
M
Subramanyam
B T
BT
Huber
R P
RP
Sékaly
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D005075:Biological Evolution; D015704:CD4 Antigens / Q000502:physiology; D016827:CD8 Antigens / Q000502:physiology; D006684:HLA-DR Antigens / Q000032:analysis / Q000502:physiology; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D016747:Minor Lymphocyte Stimulatory Antigens / Q000032:analysis; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta