The mechanism of action of murine antigen specific T cell helper factors to two synthetic polypeptide antigens under MHC control (GAT10 and (T,G)-A--L) has been analysed at the cellular level in vitro. Such factors stimulate antibody forming responses only in the presence of B cells and macrophages. Macrophages have binding sites for the factors and macrophages which have bound helper factor and antigen can activate macrophage depleted B cells in the absence of further factor or antigen. Ir gene defects have been located at the macrophage-B cell interaction in low responder strains of mice. Appropriate mouse anti-Ia sera block the binding of helper factors to macrophages indicating that the macrophage acceptor site may involve Ia antigens. The presence of Ir gene defects on B cells is currently being examined.

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