42 INTRODUCTION TO IMMUNOCHEMICAL SPECIFICITY 



TABLE 3-3 

 Cross-Reactions of Glycine-Leucine-Amino Polypeptides* 



» Landsteiner, 1945. 



'^ G = glycine, L = leucine. 



failure of the amide groups to have as strong an effect on serological 

 specificity as the free carboxyl groups have. 



Landsteiner obtained evidence that the antibodies to such complex 

 peptide haptens were at least partly directed toward the whole peptide 

 and not merely to the component amino acids. For one thing, 

 varying the order of the amino acids in the peptide made a marked 

 change, so that — GGL, — GLG, and — LGG were serologically 

 different, as were — GGGGL, — GGGLGG, and — LGGGG. 



Other evidence that antibody is directed toward the whole peptide 

 was obtained by "absorbing" an antiserum, i.e., by reacting the anti- 

 serum with heterologous antigens until no further precipitate formed, 

 and then reacting the absorbed antiserum with hapten. Suitable ab- 

 sorption of an antiserum for GGLGG left antibodies which reacted 

 with the homologous hapten but not with related haptens, except for 

 a slight reaction with —LGG. Tests made for comparison with diluted 

 antiserum showed that this change in reactivity was not due merely 

 to diminution in total antibody content. 



A third line of evidence came from inhibition experiments. Land- 

 steiner found that antibodies to a given peptide were generally better 

 inhibited by homologous than by heterologous hapten, even when they 

 reacted with a heterologous antigen (Table 3-4). 



From the evidence that antibodies can be directed toward the 

 whole of a peptide containing as many as five amino acids we may 

 conclude that the antigenic determinants in natural proteins may be 

 as large as this. Nevertheless, there seems to be a limit to the size 

 of the antigenic determinant to which the combining group of a 

 single antibody molecule can be directed, for Landsteiner and van 

 der Scheer (1938) found that when they used symmetrical aminoiso- 



