Possible T4-HLA class II interaction as an essential event in antigen-specific helper T lymphocyte-dependent B cell activation.
We have previously shown that the interaction between influenza virus-specific helper T lymphocytes and B lymphocytes is HLA class II restricted (Fischer, A. et al., Eur. J. Immunol. 1985. 15: 620). In the present study, we used a panel of antibodies specific for the T4 and HLA-DR molecules to investigate the role of both structures in T-B lymphocyte interaction. Several anti-T4 monoclonal antibodies were shown to block the in vitro antibody production to A/Bangkok influenza virus while they were unable to inhibit the A/Bangkok-induced proliferation of specific helper T cell clones. Some anti-HLA-DR monoclonal antibodies inhibited the antibody production to A/Bangkok, the target of the inhibition being either monocytes or B lymphocytes. The incubation of helper T cell clones with an infra-inhibitory concentration of anti-T4 antibody and of B lymphocytes with an infra-inhibitory concentration of anti-HLA-DR antibody resulted in a mutual enhancement of inhibition. Such synergistic interactions were not observed using combinations of anti-T4 and anti-B membrane structures such as p35 or LFA-1 or anti-HLA-DR and anti-T membrane structures such as T11 or LFA-1. First, these results indicate that the T4 molecule plays an essential role in T-B cell interaction even when it is not absolutely required for T cell proliferation. Second, they strongly suggest that the T4 molecule directly interacts with HLA-DR at the B cell surface. Whether such interaction is required to enhance the stability of T3/T cell receptor-antigen plus HLA class II association or whether T4-HLA-DR may transduce a signal towards B lymphocytes that is required in B cell activation remains unknown.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D009975:Orthomyxoviridae / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D006681:HLA-D Antigens; D006684:HLA-DR Antigens