Studies of antigen-RNA and immunity

Summary This review is about the involvement of antigen, and more specifically that of antigen-RNA complexes, in the inductive phase of an immune response. Early studies are reviewed that were begun by the senior author more than twenty years ago to probe the question of the role of antigen in antibody production in rabbits. It was shown that the quantity of antigen declined with time after injection but persisted at significant levels for very long intervals of time after injection, suggesting that all the antigen may never be lost. Since the liver yielded more detectable antigen than any other tissue it was the main source of in vivo antigen for biological and chemical characterization. As more extensive experiments were undertaken these showed stability of the radioactive hapten labels used to detect antigen and also the dynamic involvement of the liver in handling antigen. A body of evidence was thus accumulating that implied, at least indirectly, an immunological role for the liver-retained antigen. As for the antigen findings, one of the earliest was that antigen persisted, not in the original form of the injected protein, but as antigen fragments associated with ribonucleic acid, from whence originated the term antigen-RNA complexes. In later studies that utilized deproteinizing techniques, aimed at obtaining pure ribonucleic acid, antigen peptide was found to persist as a moiety of the isolated nucleic acid, thus providing convincing evidence for the in vivo origin of these complexes. The antigen-RNA complexes were immunologically active by both in vivo and in vitro tests. Recent experiments, using rats injected with aniline-azo-BSA have extended the earlier findings and it is these studies upon which attention will be focused in the experimental section. Liver polysomes and isolates of pure hepatocytes have been found to contain antigen material associated with RNA, and studies are in progress using these sources of material for elucidation of antigen-RNA function. It seems timely to suggest that an equally important application may be the use of these products of in vivo metabolism as probes to study the many inductive phenomena in an immune response.Abbreviations Ag antigen - BGG bovine gamma globulin - BSA bovine serum albumin - cFA complete Freund's adjuvant - ³H-BGG ³H-aniline-azo-BGG - ³H-BSA ³H-aniline-azo-BSA - ³H-RSA ³H-aniline-azo-rat serum albumin - ip intraperitoneal - iv intravenous - KLH keyhole limpet hemocyanin - np nucleopeptide - RSA rat serum albumin - ³⁵S]-BSA ³⁵S]-sulfanilate-azo-bovine serum albumin - S-BSA sulfanilate-azo-bovine serum albumin