Generation of helper T cells that recognize a cross-reactive idiotype through a network mechanism.

T cells that recognize the cross-reactive idiotype expressed on the heavy (H) chain of M104E (IgM, lambda 1) were induced in BALB/c mice by immunization with Dextran B-1355. T cells derived from mice immunized with 1 mg of Dextran B-1355 showed a marked proliferative response against M104E, whereas T cells from mice immunized with Ficoll or lesser amounts of Dextran B-1355 did not. BCL1Id, which had an immunoglobulin isotype identical to M104E, did not induce proliferation of the T cells. These T cells also proliferated against J558 (IgA, lambda 1) which shared the cross-reactive idiotype of the anti-alpha (1----3) glucosidic linkage antibody with M104E on the H chain. The T cells proliferated more efficiently against F(ab')2-104E, Fab-104E and H104E, the H chain of M104E, than against intact M104E. The T cell proliferative response against the idiotype on M104E or even H104E required macrophages as antigen-presenting cells (APC) and the response was inhibited when APC were treated with NH4Cl or chloroquine, inhibitors of antigen processing. Moreover, anti-CD4 antibody or anti-Ia antibody inhibited the proliferative response. These results indicated that anti-idiotypic T cells of the helper type, which recognized a cross-reactive idiotype associated with Ia molecules in processed form, could be induced physiologically through a network mechanism.