[A new instruction theory: possibility of a reverse flow of information from polypeptide sequences to RNA particularly in antibody synthesis, and the mechanisms of tolerance induction and immunosuppression (author's transl)].

A new instruction theory for antibody formation is presented. The reverse flow of information from the amino-acid sequences of small antigenic determinants to an antideterminant RNA (aRNA) seems feasible. Prerequisites are specific activating enzymes, tRNAs, ATP as well as some kind of membrane assembling the anticodons of tRNAs linearly, analogous to the linear primary structure of stretched polypeptides. Once synthesized, aRNA might be replicated, utilized as transfer factor and transcribed by means of Reverse Transcriptase into aDNA. Further steps would be the fusion of this aDNA with genetical performed DNA-molecules already coding for the basic strucures of different classes of immunoglobulins by means of a terminal deoxynucleotidyl-transferase. This could be a chromosomal or extrachromosomal integration. The second hypothesis concerns antigen-induced immunosuppression and the phenomenon of nonresponsiveness (tolerance). An overwhelming proteolysis might give rise to a degradation of antigens or receptor templates for antigenic determinants located on the surface of macrophages. On later exposure to a similar antigen proteolytic enzymes are already preformed abolishing rapidly antigenic information. The third hypothesis concerns antibody-induced immunosuppression and tolerance. Antideterminant information is integrated into the genome or established extra-chromosomally. The continuous presence of antibodies sets in motion a sequence of reactions causing an accumulation of all information intermediates including a complementary DNA strand to the aRNA. On exposure to the corresponding antigen aRNA is transcribed. However, translation might be inhibited by hybridisation with the complementary aDNA strand as well as specific RNA hydrolysis by RNase H. Concerning the immunogenity of antibodies, a proteolytical mechanism might also be possible. Taking this into account a tolerance could be suspended in the following way: 1. by influencing the overwhelming proteolytical degradation of antigenic determinants with simultaneous antigenic stimulation; 2. by substitution of aRNA to induce blocked antibody synthesis.