Characterization of "regulatory" idiotope-specific T cell clones to a monoclonal anti-idiotypic antibody mimicking a tumor-associated antigen (TAA).

As reported previously, 3A4 is a paratope-specific anti-idiotypic mAb and induces cellular and humoral anti-tumor-associated Ag (TAA) responses. In this study, the specificity, MHC restriction and Ag processing requirement of Th cell lines and clones were determined that recognize an idiotypic determinant (Id) on 3A4. The anti-Id-3A4 is part of a tumor-associated idiotypic network which is involved in the regulation of the immunity against the DBA/2 L1210/GZL tumor. These 3A4-Id-specific T cell clones are phenotypically Th cells and recognize Id in the context of MHC class II molecules under MHC restriction. Moreover, the recognition of Id by these T cell clones is chloroquine sensitive, suggesting that they recognize processed Id. However, the 3A4-Id-specific T cell clones respond only to 3A4 and not to TAA. Because these clones do not recognize TAA, their biologic role in antitumor immunity could be as regulatory T cells involved in the idiotypic network regulation.