Antigen recognition by T cells. II. Intravenous administration of native or denatured ovalbumin results in tolerance to both forms of the antigen.

In the accompanying report, suppressor T cells were demonstrated that did not recognize cross-reactivity between native and denatured ovalbumin (N-OVA and D-OVA). Here we show that the T cell tolerance induced by i.v. injections of antigen does detect cross-reactivity between N-OVA and D-OVA. Mice that had been immunized with either N-OVA or D-OVA in adjuvant could be rendered profoundly unresponsive if either N-OVA or D-OVA, but not an unrelated protein, were injected i.v. Cross-tolerance was observed in assays of antigen-induced T cell proliferation and helper T cell activity. Tolerance was distinguished from suppressor T cell activity by three criteria: 1) specificity for N-OVA and D-OVA, 2) sensitivity to abrogation by cyclophosphamide, 3) duration of effectiveness. These results confirm observations made by others that suggest that tolerance is mediated by an additional mechanism(s) other than suppressor T cells. Based on a hypothesis that cross-reactivity between native and denatured antigen is related to macrophage processing of antigen, these data also suggest a critical role for processed antigen in the induction of tolerance when antigen is administered i.v.