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.
We described a T suppressor factor made by an I-J- Ly-2 T cell (Ly-2 TsF) that expresses biological activity only when its acceptor cell shares H-2-linked polymorphic genes with the cells that made the Ly-2 TsF (or when the producer cell had differentiated in a thymic environment where the gene products of the acceptor cell were expressed). The Ly-2 TsF requires the presence of I-J+ Ly-1 cells in the assay culture to express its suppressive activity, although removal of the I-J+ Ly-1 cells in the assay cultures with an I-J+ soluble factor derived from them. This I-J+ molecule not only fails to bind antigen but is also antigen nonspecific in that it can come from Ly-1 cells making factors of irrelevant specificities. For the I-J+ molecule to replace the activity of the I-J+ Ly-1 cell in the assay population, in restoring suppressive function in cultures depleted of I-J+ Ly-1 cells, it must share genetic polymorphisms linked to the I-J subregion with the Ly-2 TsF and genetic polymorphisms linked to Igh-V with the target cell. These results indicate that an I-J+ antigen-nonspecific molecule combines with an antigen-specific Ly-2 TsF via an I-J- anti-I-J "type" of interaction. The resultant molecular complex is focused on a cell surface receptor of the acceptor cell. This focusing event is controlled by the antigen-nonspecific I-J+ molecule, and the precise interaction with the receptor on the acceptor cell is controlled by Igh-V-linked polymorphic gene products. The antigenic specificity of the interaction is controlled by a receptor for antigen on the I-J- component of the complex. Thus, three focusing events are required for Ly-2 TsF to express biologic activity: (a) the Ly-2 TsF must be focused on an acceptor cell that has the same antigenic specificity (most likely via an antigen bridge); (b) it must also be focused onto an I-J+ antigen-nonspecific molecule that we refer to as a "schlepper" molecule (most likely via an I-J anti-I-J bridge); and (c) the schlepper molecule must focus the molecular complex on an Igh-V-controlled receptor on the antigen-specific target cell.
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D008040:Genetic Linkage; D006183:H-2 Antigens / Q000235:genetics; D007165:Immunosuppression Therapy; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D011110:Polymorphism, Genetic; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D013491:Suppressor Factors, Immunologic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D006183:H-2 Antigens; D008222:Lymphokines; D013491:Suppressor Factors, Immunologic