Helper T cells recognize antigen and macrophage surface components simultaneously

Abstract

ALTHOUGH the T-cell antigen receptor has been shown to be as highly specific for antigen as the immunoglobulin receptor of B cells, considerable evidence suggests that genes other than those which code for immunoglobulins are involved in the recognition of antigen by T cells. Research in this area has centred on the role of gene products of the major histocompatibility complex (MHC), in particular of the I region of the H–2 complex of mice, in the antigen-specific receptor of T cells^1–3. Other evidence has suggested that the specificity of T cells is determined by the simultaneous recognition of antigen and MHC cell-surface components. The best evidence for this comes from experiments with mice in which T-cell cytotoxic effectors specifically raised to the H–Y (ref. 4) or other minor histocompatibility antigens⁵, viral antigens⁶ or the hapten trinitrophenol (TNP)⁷ were shown to recognise simultaneously both the antigen and the products of the D or K locus of H–2 expressed on the target cells. Investigations of the role of MHC gene products in the antigen–mediated interaction of T cells with B cells or macrophages (MΦ) can be interpreted similarly^1,8–15. We present here evidence that in the mouse, helper T cells primed with the antigen, keyhole limpet haemocyanin (KLH), bound to the surface of MΦ, simultaneously recognise KLH and genetically controlled surface components of the MΦ. The rationale for our approch was as follows. In F₁ animals whose parents differ at loci controlling surface components (for example, H–2, Mls), if T cells could be primed with antigen bound to MΦ from one or the other parent, they should then cooperate preferentially with parental B cells and MΦ of the type used for priming.