%0 Journal Article %A Lemke, Hilmar %D 2016 %I Begell House %K clonal selection theory, idiotypic regulation, Self, Non-Self, B cell receptor, T cell antigen receptor, regulatory T cells, regulatory B cells, T cell vaccination %N 1 %P 13-56 %R 10.1615/CritRevImmunol.2016016606 %T Antigen Receptor−Intrinsic Non-Self: The Key to Understanding Regulatory Lymphocyte−Mediated Idiotypic Control of Adaptive Immune Responses %U https://www.dl.begellhouse.com/journals/2ff21abf44b19838,056a8aee0e472557,12ef32dc0e6628ce.html %V 36 %X The clone-specific or idiotypic characters of B as well as T cell antigen receptors (BCRs/TCRs) are associated with (1) the third-complementarity−determining regions (CDR3s) that are created during V(D)J recombination (they scarcely occur in antibody light chains) and (2) BCR idiotopes created by somatic hypermutations (SHMs) during immune responses. Therefore, BCR/TCR idiotypic sites are antigen receptor−intrinsic Non-Self (AgR-iNS) portions that fulfill two tasks: serving as a crucial component of the epitope-binding paratope and serving as target sites for anti-idiotypic BCR/TCR paratopes of other anti-Non-Self clones that are contained in both normal repertoires. The antigen-induced immune response is thus directed not only toward the environmental stimulus but also against the AgR-iNS portions of the directly and further activated clones that form a subsiding idiotypic cascade. These idiotypic chain reactions form a completely integrated idiotypic control circuit among B and T cells which contains all regulatory T and B cells. However, this circuit cannot be viewed as a network of fixed interacting nodes but rather uses the genetic Self as reference. Hence, AgR-iNS offers a mechanistic understanding of regulatory lymphocyte−mediated idiotypic control of adaptive immune responses and reconciles clonal selection and idiotypic network theories hitherto believed to be incompatible. %8 2016-07-28