Biochemical and immunological studies on cellular components of tubercle bacilli

Abstract

1. Antigenic Proteins and Their Related Proteins of Mycobacteria: Sadamu NAGAI (Toneyama Institute for Tuberculosis Research, Osaka City University Medical School) 2. Cord Factor and Related Glycolipids: Ikuya YANO (Department of Microbiology, Osaka City University Medical School) 3. Immunological Properties of Muramyldipeptides (MDP) and Related Synthetic Compounds: Ichiro AZUMA (Institute of Immunological Science, Hokkaido University) 4. Antitumor Activity of Mycobacterial DNA: Tetsuro KATAOKA, Saburo YAMAMOTO, Toshiko YAMAMOTO and Tohru TOKUNAGA (National Institute of Health Tokyo) tubercle bacilli were extensively carried out by the support of molecular biology and basic immunology. In this symposium, recent advances in these fields, especially the antigenic protein of tubercle bacilli, biological activities of cord factor (trehalose dimycolate, TDM), immunopotentiating activity of muramyldipeptide (MDP) and antitumor activity of DNA were reported. In last decade, a variety of antigenic proteins of mycobacterial cells and culture filtrate were purified and their amino acid sequences were determined by using molecular gene technology. Dr. Nagai reviewed the biochemical and immunological properties of MPB 70, 12 kDa protein, a antigen and 65 kDa protein. Cord factor (trehalose-6, 6‘-dimycolate, TDM) has been purified from pathogenic tubercle bacilli as a toxic glycolipid. Recently, several biological activities including immunoadjuvant activity of TDM were reported and a variety of TDM related compounds were chemically synthesized. Dr. Yano summarized his recent results on the chemical polymorphism of TDM and trehalose monomycolate (TMM) and their biological activities such as toxicity, activation of alveolar macrophages, antitumor activity, cytokine induction, etc. It is well known that tubercle bacilli are potent immunostimulant and immunoadjuvant activities of the several cellular components of mycobacterial cells such as cell—wall skeleton (CWS), TDM, DNA fraction and muramyldipeptide (MDP) were extensively examined. MDP was reported to be the minimal adjuvant—active subunit of CWS and several hundred MDP derivatives and related compounds for the immunostimulants were chemically synthesized. Dr. Azuma and his group developed MDP derivative, MDP-Lys(L18), as a cytokine inducer. MDP—Lys(L18) induces several cytokines such as IL—1, IL—6, TNF, CSF, etc. and was shown to be effective for the restoration of decreased number of leukocytes and platelet in the cancer patients who were treated with cancer chemotherapy and radiation therapy. The detailed mechanism of action of MDP-Lys(L18) was also discussed. The antitumor activity of cellular components of tubercle bacilli is well established in experimental tumor systems and clinical trials. Dr. Kataoka and his associates reported that DNA fractions (MY—1) of tubercle bacilli was a candidate of cancer immunotherapeutic agent. By the biochemical analysis of MY—1 and chemical synthesis of related oligonucleotide, Dr. Kataoka's group developed synthetic oligo—DNA nucleotides having the stimulating activity of NK cell function. The future aspects of the biochemical and immunological studies on mycobacterial fractions were also discussed. © 1992, JAPANESE SOCIETY FOR TUBERCULOSIS. All rights reserved.