Interactions between molecules (subfactors) released by different T cell sets that yield a complete factor with biological (suppressive) activity.

T cells that have been immunized to express optimal levels of contact hypersensitivity upon adoptive transfer to normal animals can be inhibited from doing so by incubating them with an antigen-specific T suppressor factor. This factor is composed of at least two subunits which come from cells expressing different Ly phenotypes; an antigen-specific antigen-binding "subfactor" is made by an Ly-1 cell and a non-antigen-binding one is made by an Ly-2 cell. Neither of these cells nor their products express detectable amounts of major histocompatibility gene products. The mode of immunization plays an important role in determining which of these subfactors will be produced. Painting the skin with a reactive hapten immunizes Ly-1 cells that secrete antigen-binding material, whereas intravenous injection of trinitrobenzenesulfonic acid activates Ly-2 cells to produce a second subunit that does not see antigen. There is reason to believe that the molecule that does not bind to antigen does have some antigen specificity. An analysis of the data at hand suggests that the antigen specificity stems from an interaction of the two subunits described with yet another subunit and that biological activity is dependent upon three macromolecules. Thus, the complex level of cellular interactions that regulate immunity may also be reflected in a similar type of complexity in the interaction between their biologically active cell-free products.