免疫系の分子遺伝学 : 基礎と臨床

NDLデジタルコレクション NDLデジタルコレクション

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タイトル別名
  • Molecular Genetic Studies on the Immune System : An Approach to Clinical Application

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It is the function of the immune system to recognize and neutralize numerous antigens invading animals. The more diverse the antigen recognition of the organism, the more efficient is its defense system. There are two types of antigen recognition molecules in the immune system ; the immunoglobulin produced by B cells and the T cell antigen receptor. These molecules have variable (V) regions which recognize antigens and constant (C) regions which mediate physiological functions. The latter provide additional diversity to the immune system. For example, the same heavy chain (H) V regions recognizing influenza hemoagg-lutinin are expressed as the μ, γ, ε, and a chains, each of which constitutes a different class of the immunoglobulin. Since the V and C regions are encoded by separate sets of DNA segments, it is the genetic variability of the V gene that determines the antigen recognition diversity. Recent molecular genetic studies on the immunoglobulin gene and the T cell antigen receptor gene indicate that the V region genes of both molecules produce somatic as well as evolutionary variations. Somatic variations include joining of two or three germ-line segments by site-specific recombinations and somatic base replacements. Evolutionary variations include gene duplication, segment transfer (gene conversion), mutational drifts, and so on. Since genetic events, be it somatic or evolutionary, tend to be random, not only useful but also harmful immunog-lobulins are produced. Therefore, appropriate selection, be it positive or negative, is a prerequisite for the proper function of the genetic diversity of the immune system as the defense mechanism. Combination of genetic veriability and appropriate selection is the basic idea to explain biological diversity since Darwin and Wallace, and was applied to the immune system by Jerne and Burnet as the clonal selection theory which still remains valid in essence. The basic questions to be asked are : (a) How are genetic variants of the immunoglobulin and T cell receptor genes created ? and (b) How are the variants selected ? I have summarized recent knowledge of the origin of genetic variations of the immunoglobulin and T cell antigen receptor,or genes. Then I described my personal view of the selection mechanism which remains a matter of controversy. I have overviewed our recent studies on the lymphokine and its receptor which plays essential roles in antigen-specific proliferation of lymphocyte clones. Particularly, cloning and characterization of cDNAs for the IL-2 receptor and IL-4 (BSF-I) were described. Finally, a genetic strategy to construct chimeric antibodies carrying murine V and human C regions was explained.

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