Studies on the chemical basis of the antigenicity of proteins. 2. Antigenic specificity of polytyrosyl gelatins.

In the preceding paper it was shown that the attachment of tyrosine, tryptophan or phenylalanine peptides to gelatin converts it into a relatively powerful antigen. The serological specificity of these gelatin derivatives varied according to the nature and the length of the peptides attached. Thus the specificity of polytyrosyl gelatin (10% of tyrosine residues) and polytryptophyl gelatin (25% of tryptophan residues) was due, respectively, to polytyrosine and polytryptophan chains, but not to gelatin. On the other hand, with polyphenylalanyl gelatin (9 % of phenylalanine residues), it could be shown that the specificity is associated not only with the phenylalanine chains but also with gelatin itself. In view of these findings it seemed of interest to enquire how the potency of the new antigens depends on the number of amino acids attached to gelatin. By enhancement or increase in antigenicity we understand an increase, relative to gelatin, in the eliciting of antibodies by these antigens, even if they are serologically different. It also seemed worthwhile to examine the change in the serological specificity of polypeptidyl gelatins as a function of the length of the polypeptides attached. In this paper we report the results of an investigation of the extent of antigenicity and the antigenic specificity of a series of polytyrosyl gelatins differing in their tyrosine content. We have found that the attachment of 2% of tyrosine to gelatin suffices to convert it into a relatively strong antigen. Yet the specificity of this antigen is due mainly to gelatin. In view of the assumed role of polar groups in the antigenic specificity of proteins, we have also investigated the antigenicity of gelatin enriched with copolymers of tyrosine and glutamic acid. Although the attachment of polar amino acid residues alone does not significantly enhance the antigenicity of gelatin (Sela & Arnon, 1960), glutamic acid in company with tyrosine affected both the extent and the specificity of the immunological response.