Hypotheses on a germline origin of antibody diversity. Possible applications: improvement of the efficiency of immune response and autoimmune disease treatment.
In this paper, the antibody reaction is supposed to be due to the combination of a limited number of different antibodies against the epitopes of the antigen. In addition, the efficient part of the epitopes of proteins is assumed to be the size of dipeptides. The 400 different dipeptides would be distributed in two sets, those which are foreign to the host, against which would be directed antibodies, and those which are present in the proteins of the self, which would elicit no reaction. Each chain of the antibodies would recognise one aminoacid and 40 genes would be sufficient (20 for the light chains and 20 for the heavy chains) to code for the variable parts of the immunoglobulins against proteic antigens. With these hypotheses, the combination of antibodies against at least four different epitopes of the size of dipeptides can account for the main characteristics of the antibody reaction: response against any foreign proteic antigen and specificity. In fact, the epitopes have been found to be larger than dipeptides, several additional aminoacids are involved in the antibody-binding sites. Somatic mutations and VDJ recombinations are selected to give the maximal affinity for the antigens. However, these mechanisms have not been shown to create different specificities from the same V genes. Moreover, the phenomenon of heteroclisis and the decrease, due to mutations, of antigen-binding capacity of antibodies, sometimes observed, are better explained by the model proposed here than by the classical theory. The modification of the epitope subset of the self, by intrathymic injection of antibodies against particular pathogens, is proposed to improve the immune response when microorganisms develop immune escape mechanisms. On the other hand, in the case of autoimmune diseases, the displacement of autoantibodies against self-epitopes could be carried out by the injection into the thymus of specific anti-idiotypic antibodies.
ger.berger@wanadoo.fr
G
G
Berger
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007167:Immunotherapy / Q000379:methods; D008957:Models, Genetic; D018448:Models, Immunological
D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; D000939:Epitopes; D007166:Immunosuppressive Agents