8 INTRODUCTION TO IMMUNOCHEMICAL SPECIFICITY 



(Lederberg, 1959), they might be too minor to be found by the 

 presently available methods of analysis. 



Although the brilliant researches of Sanger (1956) into the se- 

 quence of amino acids in the polypeptide chain have resulted in the 

 complete elucidation of the structure of insulin and a few other 

 polypeptides, such analysis has not yet been carried very far with 

 antibodies. However, we do know that the N-terminal sequence of 

 all rabbit globuHns thus far studied, including various antibodies, 

 seems to be (Porter, 1950; McFadden and Smith, 1955) : 



Alanine- — leucine — valine — aspartic acid — glutamic acid — 

 In contrast to the uniformity of rabbit globulins, horse globulins, 

 whether antibody or normal globulin, have proved to be quite hetero- 

 geneous in this respect, all preparations exhibiting a wide variety of 

 N-terminal groups (McFadden and Smith, 1955b). The globulins 

 of man likewise differ among themselves in amino acid composition 

 (Smith et al., 1955b; Putnam, 1955). 



Pozvers of Discrimination of Antibodies 



It was long ago suspected that the cross-reactions of antibodies 

 with related antigens were due to chemical similarities between the 

 homologous and the cross-reacting antigen. But in the absence of 

 detailed information about the chemical structure of natural antigens 

 (a situation which has improved only slightly since the earliest 

 days of immunochemical work), it was not possible to state how 

 great the chemical similarity between two antigens had to be to 

 make cross-reaction possible or, to put it another way, how small a 

 chemical differences antibodies could detect. Karl Landsteiner (1945) 

 largely overcame this difficulty by the use of conjugated antigens. 



It was known that chemical treatment (nitration, iodination, etc.) 

 of protein antigens often changed the immunochemical specificity. 

 Landsteiner showed that if simple chemical compounds were coupled 

 chemically to protein antigens it was possible to produce antibodies 

 which reacted specificially with the simple free compound (which 

 Landsteiner called a hapten). Thus it was possible to observe sero- 

 logical reactions which depended only on the hapten, the structure 

 of which was known, and not on the natural protein antigen of yet 

 undetermined chemical structure. 



