IMMUNE RESPONSE TO POLYPEPTIDYL PROTEINS IN RABBITS TOLERANT TO THE PROTEIN CARRIERS
WEIZMANN INST OF SCIENCE REHOVOT (ISRAEL)
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A study was made of the immune responses to polypeptidyl proteins in rabbits which were either naturally tolerant or made experimentally unresponsive to the protein carriers. Experimentally acquired tolerance to HSA could be terminated by immunization of the unresponsive rabbits with poly-Ltyrosyl derivatives of HSA. Two parameters determined the breakdown of tolerance 1 the chemical nature of the peptides attached polytyrosyl HSA was effective in the termination of tolerance to HSA, whereas polyalanyl HSA was not 2 the degree of enrichment was tyrosine. There appears to be an optimal degree of enrichment, i.e. of molecular alteration of the HSA, which will confer on the altered antigen the maximal potency to terminate tolerance a slight alteration 3 per cent enrichment of HSA with Tyr and a severe alteration 13 per cent enrichment were less effective in tolerance breakdown than an intermediate degree of alteration 7 per cent enrichment with Tyr. The level of tolerance breakdown obtained by polytyrosyl HSA, as measured by the ratio of anti-HSA anti-polytyrosyl HSA, was greater than the level obtained previously by other chemically altered antigens. The significance of this ratio was discussed in relation to the cellular basis of immunological tolerance. Antibodies were produced to the peptides per se, when attached to proteins towards which the animal is naturally tolerant RSA, or to proteins to which the animal has acquired tolerance HSA. In both systems, there was a similar pattern of antibody formation, which may reflect a similarity in mechanism between natural and actively acquired tolerance.