Possible T4‐HLA class II interaction as an essential event in antigen‐specific helper T lymphocytedependent B cell activation

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Abstract
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 (a) anti‐T4 and anti‐B membrane structures such as p35 or LFA‐1 or (b) 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.