Two subsets of cloned T helper cells exhibit different activation requirements and characteristics.

An anti-clonotypic monoclonal antibody (mAb 211G7H) was generated against a T helper cell clone which specifically recognized type II collagen. Besides inhibiting the proliferative response of the immunizing T cell clone to type II collagen, mAb 211G7H (soluble form) also suppressed the antigen-induced proliferation of several other T cell clones which shared similar specificity for antigen and major histocompatibility complex with the immunizing T cell clone. On the other hand, mAb 211G7H did not inhibit the responses of clones exhibiting different antigenic specificities from the clonotype-positive T cell clones. It was also demonstrated that these clonotype-positive T cell clones responded differently to mAb 211G7H when it was immobilized. Based upon their proliferative responses to immobilized anti-clonotype 211G7H mAb, two subpopulations of T cell clones were defined. Collagen-specific T cell clones of the first group proliferated poorly when stimulated with immobilized anti-clonotype mAb, by contrast, T cell clones belonging to the second group proliferated well to immobilized mAb. Furthermore, upon stimulation with immobilized 211G7H mAb, the second subpopulation of cloned T cells produced both interleukin (IL) 2 and IL4, while the first group secreted IL2 but not IL4. The cloned T cells from the group which responded weakly to immobilized anti-clonotype mAb also mediated reduced proliferative responses to IL2 in the presence of immobilized 211G7H mAb. Finally, these two subsets of T cell clones were found to respond differently to other non-antigen stimuli such as IL4 and phorbol 12-myristate 13-acetate. Thus, from a panel of collagen-specific T cell helper clones which had similar receptor fine specificities, we have isolated two subsets of cloned T helper cells that displayed different activation requirements and lymphokine production.