Antigen specific T-cell helper factor cross reacts idiotypically with antibodies of the same specificity

Abstract

THE recognition system of bone marrow-derived (B) cells and their products is based on the interaction of the active site of immunoglobulins with the specific antigenic determinants. However, the molecular nature of the recognition component of thymus-derived (T) lymphocytes is not yet established. Studies on antigen specific T-cell helper or suppressor factors1–5 and isolation of the antigen receptor directly from T cells, or from serum6,7 are examples of approaches to elucidate this problem. The synthetic polypeptide poly(Tyr,Glu)-poly(DLAla)--poly(Lys) [abbreviated (T,G)-A--L] has been extensively used in studies on the molecular basis of antigenicity8 and genetic regulation of immune responsiveness9–11. Studies on the antibody response to (T, G)-A--L have revealed the involvement of several cell types and a T-cell replacing soluble factor which are antigen specific and genetically controlled12–14. An important feature of the T-cell factors is their antigen specificity. The specificity of a T-cell factor produced to (T, G)-A--L was demonstrated by the removal of its activity on specific antigen-Sepharose columns15 and also by demonstrating that the in vivo helper effect was specific to the antigen used in the T cell education1,16. It is very likely that the specific T-cell factor represents the molecular recognition component of T cells—the T-cell receptor. If this is the case, the molecular identification and characterisation of the T-cell factor may answer one of the most controversial questions in immunology. It has been suggested that antigen-specific molecules of B and T cells share idiotypic dterminants17,18. It was, therefore, of interest to find out whether the (T, G)-A--L specific factor will share idiotypic determinants with antibodies of the same specificity. The results of the present study demonstrate that B-cell products (antibodies) and T-cell products (factors) possess cross-reacting idiotypic determinants. This strongly suggests the presence of similar variable regions in both antigen binding entities, which are probably coded by the same variable region genes. Cross-reactive idiotypic determinants are also present on (T, G)-A--L specific factors obtained from low responder C3H/DiSn T cells confirming previous reports on the activity of these factors.