Antigen-binding human T suppressor cells and their association with the HLA-DR locus

Abstract

The ability of human lymphocytes to bind antigen was studied by direct binding of 125I-labeled streptococcal protein antigen, followed by autoradiography. T-enriched lymphocytes depleted of adherent cells and B cells showed specific binding of 125I-labeled streptococcal antigen (SA) at 4 degrees C and in the presence of sodium azide. Further depletions of the T-enriched population by the monoclonal T4 or T8 antiserum and complement revealed that the antigen-binding T cell is T4-, T8+. This was confirmed by positive selection of T8 cells, by rosetting with ox red blood cells and by the binding of SA by in vitro induced suppressor but not helper cells. Antigen specificity of binding to the suppressor cells was established by complete inhibition with the SA but no inhibition with keyhole limpet hemocyanin. A characteristic dose-response of binding 1 or 10 ng SA to HLA-DRw6 lymphocytes and 1000 ng SA to DR4,1,2,3 or 5 lymphocytes was found. A comparison of the dose-responses of antigen-binding T8+ suppressor cells with those of helper and suppressor functions showed that the dose of SA which binds to suppressor cells is similar to the dose required to induce helper but not suppressor function. A plausible interpretation of these observations is that the T8+ antigen-binding suppressor cells might function as "contrasuppressor cells" which compete successfully for the membrane receptors of helper cells, thereby preventing suppression by the major subset of suppressor cells.