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

Abstract

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.

Functional roles of two polypeptide chains that compose an antigen-specific suppressor T cell factor.

“…Therefore, the treatment of TsF with a reducing agent may interfere with the heterologous association of the two chains. In any event, the ability to exchange I-J-bearing chains from different haplotypes shown in our study would suggest that the association of the I-J-bearing and antigen-binding chains does not seem to be placed by an I-J anti-I-J-type interaction, as proposed by others (7,16,17).…”

Serotonin Initiation of Delayed-Type Hypersensitivity: Mediation by a Primitive Thy-1⁺ Antigen-Specific Clone or by Specific Monoclonal IgE Antibody

“…In new studies we showed that separate regulatory systems could suppress DTH through a locus of action on either the late cell or the early cell. The previously welldescribed system of Ag-specific suppression of contact sensitivity by high-dose intrave nous treatment with reactive hapten [42][43][44] was shown to affect the late cell, and not the early cell [12]. This suppression was due to the combined action of a Thy-1+.…”

Analysis of the interactions between two molecules that are required for the expression of Ly-2 suppressor cell activity. Three different types of focusing events may be needed to deliver the suppressive signal.

“…The question of whether the situation we described is unique for the suppressor molecule(s) we described, or whether it can act as a general model for other antigenspecific T cell informational molecules, must be addressed. With a very important caveat, we think that a generalization is possible for two reasons: (a) with three of three different suppressor molecules that we analyzed, two separate macromolecules are required for the deliverance of a biologically active signal (3,5). Other workers (6, 7) also report requirements for two separate chains to achieve antigen-specific biological activity; (b) the similarity between the mechanism by which the factor we described works and the way diptheria and other toxins work (1(3) indicates to us that the mechanism of action is an example of a biological generalization.…”