Immunogenetics and Immunodeficiency

The identification of the genes which determine biological phenomena, and the study of the control they exert on these phenomena, has proven to be the most successful approach to a detailed understanding of their mechanism. The greatest advances in molecular biology have relied upon the application of the methodology of genetics to the elucidation of the fundamental processes of life at the cellular level. The same statement may be made concerning our understanding of im munological phenomena. The genetic approach has again proven extremely productive and has permitted us to identify many fundamental questions in im munobiology and to resolve some of them successfully. Among the problems with which the young discipline of immunogenetics has been concerned are the structural genes of the immunoglobulin chains. These genes have been iden tified by their control of allotypic antigenic determinants on the constant seg ment of H chains of different classes, on the constant segments of L chains and on both the constant and variable regions of rabbit H chains. These studies have provided the first evidence for the control of a single polypeptide chain by two distinct structural genes. Much has been learned concerning the genes coding the C and V regions of immunoglobulin chains (a) from the study of the inheritance of allotypic and idiotypic determinants on these chains discussed by Kunkel and Kindt and (b) from the analysis of the amino acid sequence in immunoglobulin chains from individual myeloma proteins and abnormal paraproteins, discussed by Frangione.