title: Antigen Receptor-Intrinsic Non-Self: The Key to Understanding Regulatory Lymphocyte-Mediated Idiotypic Control of Adaptive Immune Responses.
abstract: 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.
authors.affiliation: Biochemical Institute of the Medical Faculty of the Christian-Albrechts-University at Kiel, D-24098 Kiel, Rudolf Hoberstr. 1, Otto Meyerhof-Haus, Germany.
authors.forename: Hilmar
authors.initials: H
authors.lastname: Lemke
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
chemical_list: D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell