The pioneering work of Karl Landsteiner in the 1920's and 1930s created a simple ,chemically defined system for studying the binding of an individual antibody antibody to a unique epitope on a complex protein antigen.Landsteiner employed various haptens,small organic molecules that are antigenic but not immunogenic hapten-carrier conjugate.Animals immunized with such a (1) The hapten determinant,(2) unalterd epitopes on the carrier protein,and(3) new epitopes formed by combined parts of both the hapten and carrier.By itself,a hapten cannot function as an immunogenic epitope.But when multiple molecules of a single hapten are coupled to a carrier(or nonimmunogenic homopolymer),the hapten becomes accesible to the immune system and can function as an immunogen.
The beauty of the hapten-carrier system is that it provides immunologists with a chemically defined determinant that can be subtly modified by chemical structures on immune specificity.In his studies,Landsteiner immunized rabbits with a hapten-carrier conjugate and then tested the reactivity of the rabbit's immune sera with that hapten and with closely related haptens coupled to a different carrier protein.He was thus able to measure,specifically,the reaction of the antihapten antibodies in the immune serum and not of antibodies to the original carrier epitopes.Landsteiner tasted whether an antihapten antibody could bind to other haptens having a slightly different chemical structure.If a reaction occurred,it was called a cross-reaction,Landsteiner was able to gain insight into the specificity of antigen-antibody interactions.
Using various derivatives of aminobenzene as haptens,Landsteiner found that the overall configuration of a hapten plays a major role in determining whether it can react with a given antibody.For example,antiserum from rabbits immunized with aminobenzene or one of its carboxyl derivatives(o-aminobenzoic acid, m-aminobenzoic acid, p-aminobenzoic acid) coupled to a carrier protein reacted only with the original immunizing hapten and did not cross-react with any other haptens.In contrast,if the overall configuation of the hapten was modified in the para position with various non-ionic derivatives ,then the antisera showed various degrees of cross-reactivity.Landsteiner's work not only demonstrated the specificity of the immune system,but also demonstrated the enormous diversity of epitopes that the immune system is capable of recognizing.
Many biologically important substances,including drugs,peptide hormones and steroid hormones,can function as haptens.Conjugates of these haptens with large protein carriers can be used to produce hapten-specific antibodies.These antibodies are useful for measuring the presence of various substances in the body.For instance,the original home pregnancy test kit employed antihapten antibodies to determine whether a womens urine contained human chorionic gonadotrophin(HCG), which is a sign of pregnancy.However,as shown in the clinical Focus,the formation of drug-protein conjugates in the body can produce drug allergies that may be life-threatening.
The beauty of the hapten-carrier system is that it provides immunologists with a chemically defined determinant that can be subtly modified by chemical structures on immune specificity.In his studies,Landsteiner immunized rabbits with a hapten-carrier conjugate and then tested the reactivity of the rabbit's immune sera with that hapten and with closely related haptens coupled to a different carrier protein.He was thus able to measure,specifically,the reaction of the antihapten antibodies in the immune serum and not of antibodies to the original carrier epitopes.Landsteiner tasted whether an antihapten antibody could bind to other haptens having a slightly different chemical structure.If a reaction occurred,it was called a cross-reaction,Landsteiner was able to gain insight into the specificity of antigen-antibody interactions.
Using various derivatives of aminobenzene as haptens,Landsteiner found that the overall configuration of a hapten plays a major role in determining whether it can react with a given antibody.For example,antiserum from rabbits immunized with aminobenzene or one of its carboxyl derivatives(o-aminobenzoic acid, m-aminobenzoic acid, p-aminobenzoic acid) coupled to a carrier protein reacted only with the original immunizing hapten and did not cross-react with any other haptens.In contrast,if the overall configuation of the hapten was modified in the para position with various non-ionic derivatives ,then the antisera showed various degrees of cross-reactivity.Landsteiner's work not only demonstrated the specificity of the immune system,but also demonstrated the enormous diversity of epitopes that the immune system is capable of recognizing.
Many biologically important substances,including drugs,peptide hormones and steroid hormones,can function as haptens.Conjugates of these haptens with large protein carriers can be used to produce hapten-specific antibodies.These antibodies are useful for measuring the presence of various substances in the body.For instance,the original home pregnancy test kit employed antihapten antibodies to determine whether a womens urine contained human chorionic gonadotrophin(HCG), which is a sign of pregnancy.However,as shown in the clinical Focus,the formation of drug-protein conjugates in the body can produce drug allergies that may be life-threatening.
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