In vitro interactions between KLH, SRBC, or (T,G)-A--L-specific helper T cells and either B cells or macrophages (Mϕ) were shown to involve the simultaneous recognition of both the antigen and a product(s) of the I-region expressed on the B cell and the Mϕ. For example, in the anti-TNP response to TNP-(T,G)-A--L, T cells from (T,G)-A--L primed high × low responder F1 mice required that both high responder B cells and Mϕ be present in culture for a high response. Thus, it was surprising that KLH or SRBC primed T cells from F1 mice whose parents differed at H-2 could interact equally well with Mϕ-depleted B cells from either parent, regardless which parental Mϕ was used to reconstitute the cultures.

One possible explanation for these results was that effective responses required two synergising antigen-specific, I-specific helper T cells, one of which interacted with antigen bound to the Mϕ, and the other of which interacted with antigen bound to the B cell.

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