Tolerance to thymus-independent antigens. Characteristics of induction of tolerance to thymus-independent synthetic polypeptides.

The conditions have been studied for induction of tolerance in mice to two thymus-independent multichain synthetic polypeptides, poly(DTyr,DGlu)-polyDPro--polyDLys, and poly(DTyr,DGlu)-polyLPro--polyLLys. The antigens are of very similar structure, differing only in the optical configuration of proline and lysine residues. The tolerance thresholds were established by giving a single injection of antigen in solution in saline, followed later by challenge of antigen in adjuvant. For both antigens it was possible to induce high dose tolerance, which was preceded by a zone of priming at lower doses. In neither case was low zone tolerance observed. The induction of high zone tolerance was accompanied by a passing phase of antibody production in the case of poly(DTyr,DGlu)-polyDPro--polyDLys, but not in the case of poly(DTyr,DGlu)-polyLPro--polyLLys. Furthermore, the threshold doses for high zone tolerance for the two antigens differed by two orders of magnitude, being at about 100 μg per mouse for the former and at 1 μg per mouse for the latter. It appears that thymus-independent antigens, even if very similar structurally, can differ very markedly in the characteristics of their interaction with B cells.