38 INTRODUCTION TO IMMUNOCHEMICAL SPECIFICITY 



Anti(/cnic Determinants 



Antibodies combine with the surface of antigenic cells or mole- 

 cules. Even an antigen molecule of only moderate size can combine 

 with several molecules of antibody. This shows that the portion of 

 the antigenic surface toward which the antibody is directed (anti- 

 genic determinants) is only part of the whole molecule. In Chapter 

 1 we saw that antibodies can be produced which combine specifically 

 with relatively small molecules such as arsanilic acid or glucose. The 

 cjuestion arises : How much of the surface of a antigen molecule is 

 actually involved in the combination with antibody? 



Some information on this question has been obtained, mostly by use 

 of Landsteiner's inhibition technique. Landsteiner (1942) found 

 that hydrolysis products of silk, peptides with molecular weights about 

 600 to 1000, were capable of specifically inhibiting the reactions or 

 precipitin sera for silk. This work has recently been confirmed by 

 Cebra (1961), who found that tyrosine forms an important part of 

 the antigenic determinant in silk fibroin, but that a considerable 

 length of the glycyl-alanyl chain is also required for detectable 

 specific combination. Dodecapeptides (MW ca. 900) were the most 

 active of the peptides compared, giving up to 50 per cent inhibition. 

 Of the octopeptides tested, Gly (Glys, Alas) Tyr (MW ca. 600) 

 was the most effective inhibitor and probably represents a major 

 part of the specific antigenic determinant. 



Better evidence comes from reactions with conjugated antigens con- 

 taining complex haptens. From quantitative studies of the inhibition of 

 antibodies to simple haptens Hooker and Boyd (1933, 1941) concluded 

 that the specificity of the antibody was influenced to some extent by 

 the protein tyrosine or histidine residues with which the diazotized 

 amines combine. This suggested that the antigenic determinant in 

 conjugated antigens is not quite as simple a structure as the hapten 

 alone (Fig. 3-2). Landsteiner (1945) studied the question by coupl- 

 ing to proteins haptens containing peptides made up of several 

 amino acids. Goebel, Avery, and Babers (1934) and Kabat (1957) 

 investigated antibodies directed toward determinants consisting of 

 several sugar molecules linked together to form an oligosaccharide. 

 Let us review some of these experiments briefly. 



Peptide Determinants. Since some proteins are made up entirely 

 of amino acids, and since there is no evidence that the specificity of 



