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F., Kallmeyer C., Pritchard-Jones K., Durrant L. that has the potential for innovation in terms of rational design of reagents with biological, chemical, and pharmaceutical applications that underlies concepts of reverse immunology which is highlighted herein. Keywords: anti-idiotype, carbohydrate mimetic peptides, idiotype network theory, cancer, tumor, mimotopes, antibody, vaccine design INTRODUCTION Scientific concepts can spring up now and then that captures the attention of scientific thought, only to be replaced by new ideas (Bornholdt et al., 2011). However, some concepts remain latent for years waiting to be rediscovered. Interestingly, this phenomenon has been modeled mathematically based on cooperative events in the evolution of ideas. The modeling suggests that systems with high innovation rates tend to contain a high degree of noise, along with many small domains of ideas that are constantly generated and replaced. In contrast, systems with low innovation rates tend to have low noise and a PF-06371900 state that remains dominant for a long time until a single event replaces it (Bornholdt et al., 2011). Immunology seems to operate on two gears. At the system level, it is of a low innovation type with just a couple of theories slowly rising and/or falling over its lifetime of about a century. At the level PF-06371900 of its bordering with molecular biology and cellular physiology, the avalanche of data spurs a much more intense Mouse monoclonal to GRK2 flow of parallel concepts, e.g., mechanisms of antigen receptor repertoire generation, cytokine networks, suppression, lymphocyte population structure, etc. PF-06371900 These are concepts that emerge often in PF-06371900 loose relationship to each other as they address different domains of the immune system. Although of local importance, they often become fashionable and temporarily generalized, attempting to explain more than they can. This is due, at least in part, to the big theories having a hard time catching up because of their slower development. One such concept is the idiotype network theory (INT) brought forth by Jerne (1974), 1984. The INT postulates that a population of antibodies forms a hierarchical and dynamic network of interconnected elements that define the regulation of the immune system. The promise of the anti-id concept lies in (1) elucidating the immunological mechanisms associated with the regulation of the immune response, (2) defining how nature developed its own approach to reverse engineering which is applicable to vaccine design, (3) their use as vaccines and immunotherapeutics, and (4) their utility in understanding self-tolerance and control of lymphocyte homeostasis. THE FOUNDATION OF THE STORY The basis of the INT is the concept of the idiotype (Id). An Id is a shared characteristic between a group of B cells (immunoglobulin) or T cell receptor (TCR) molecules based upon the antigen binding specificity, and therefore structure of their variable region. The variable region of TCRs and immunoglobulins contain complementarity-determining regions (CDR) with unique amino acid structure that determines the antigen specificity of the receptor. The structure formed by the CDR is known as the idiotope. The term Id is often used to describe the collection of multiple idiotopes, and therefore overall antigen binding capacity, possessed by an antibody. Immunoglobulins or TCRs with a shared idiotope are the same Id. The antibody Id is determined by gene rearrangement, junctional diversity, palindromic nucleotides at sites of single-strand breaks, N-nucleotides, and somatic hypermutations. Inherent to the INT is the relationship between the combining site (paratope) for antigen and the expression of an Id (idiotope). The Network Theory of Jerne postulates that the immune system functions as a regulatory network that is comprised of Ids (Ab1s) and their anti-Ids (Ab2s) in which B cells and other antigen-presenting cells (APC) provide for antigen processing (Figure ?Figure11). The inherent relationships of the network hierarchy activate both B and T cells through idiotypic network determinants that mimic the three-dimensional structure of the nominal antigen, and thereby activate Ab1 precursors reactive with foreign or self-antigens. They may also be responsible for the stimulation and maintenance of memory T lymphocytes. Thus, MHC-restricted T cells appear to recognize immunoglobulin by the same rules as those that apply to recognition of proteins in general. Antibody Ab1, synthesized in response to a primary antigen, in turn elicits a secondary antibody Ab2. B cell clones recognizing idiotopes on Ab1 in the generation of Ab2s are a heterogeneous population displaying multiple specificities. Sometimes, immunization with Ab2 induces antibodies (Ab3s), which resemble Ab1s as induced by.