Determinants of antigenic molecules responsible for genetically controlled regulation of immune responses.

The ability of mice bearing the H-2S haplotype to develop helper responses to the random copolymer of Glu,Ala while they developed suppressor responses to the terpolymer of Glu,Ala,Tyr suggested the crucial role of tyrosine in these peptides. On the basis of various considerations, it was postulated that many of the tyrosine residues in Glu,Ala,Tyr would be localized at the NH2-terminal end of the molecule. To verify this hypothesis, a block terpolymer composed of a short sequence of homopolymer tyrosine covalently bound to the random copolymer of Glu,Ala was synthesized. The present studies, using this block terpolymer, demonstrated that the chemical determinants stimulating helper and suppressor responses are distinct and can be present simultaneously in the same molecule. Thus, addition of COOH-terminal tyrosine residues to the Glu,Ala polypeptide converted this immunogenic molecule to an immunosuppressive molecule in mice bearing the H-2S haplotype. The mechanism by which these short sequences of tyrosine influence H-2-linked immune responses remains to be determined.