ANTIBODY STRUCTURE AND THE IMMUNE RESPONSE

1974 ◽  
pp. 1-6
Author(s):  
Henry Metzger
1966 ◽  
Vol 166 (1003) ◽  
pp. 188-206 ◽  

Recent advances in molecular biology have permitted significant progress in correlating the chemical structure and biological function of naturally occurring macromolecules. The problem of the nature and mechanism of the immune response is a field of molecular biology which still poses many difficulties at both the cellular and the molecular level. The heterogeneity of antibodies is an outstanding example of these difficulties. One of the approaches to a better understanding of the chemical basis of immunological phenomena was the use of simple and well-defined molecules as elicitors of the various types of immune response. The use of synthetic polypeptides, polypeptidyl proteins, and of conjugates of various small molecules with synthetic polypeptides in studies of the molecular basis of immunological phenomena (for review, see Sela 1966) facilitates, due to the relative simplicity of these antigenic models, the interpretation of results obtained with them and sometimes permits the detection of differences, such as genetic variations in the capacity to produce specific antibodies (Levine, Ojeda & Benacerraf 1963; McDevitt & Sela 1965), which are not observable with complex natural antigens. Antibodies directed toward synthetic polypeptides may prove useful in studies of the antibody structure and biosynthesis, as it should be possible to correlate differences between the antibodies with the known differences between the synthetic antigens.


1966 ◽  
Vol 164 (995) ◽  
pp. 320-327

A large body of data has now been accumulated concerning the ways in which heritable mutations can affect protein structure. Such mutations are usually presumed to arise in the germ line, and are studied by progeny analyses of various types. Today, I would like to consider how somatic mutations might be genetically predisposed and thereby made available to an organism during its adaptation to environmental hazards or during its development. The highly specialized immune system of higher animals can profitably be discussed from this viewpoint, and I shall describe a possible molecular mechanism (Smithies 1965) for implementing the immune response, and then consider very briefly its relevance to other adaptive and developmental processes. The immune response The essential questions which are posed by the immune system can be stated simply: (i) How can many different antibodies be specified by an initially fixed genetic endowment? (ii) How can selection be made against anti-self antibodies and for anti-foreign antibodies? (iii) How can an antigen instruct the organism to respond more effectively to repeated encounters with the same foreign substance? (i) Antibody variability could be the consequence of the organism having a relatively large number of related but not identical genes in the initial zygote from which to select combinations forming useful antibodies. This possibility is un­attractive for reasons of economy, and such a system would probably be genetic­ally unstable. I have consequently preferred to explore one of many alternative possibilities, namely that there are a limited number of genetic loci determining antibody structure which have evolved so that they can provide many different proteins as a result of genetically predisposed somatic mutations.


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