Epitopes

AbstractT‐ and B‐cell epitopes differ fundamentally in the way they are recognized by the immune system. B‐cell epitopes are recognized as three‐dimensional structures on the surface of native antigens. T‐cell epitopes are parts of internalized and processed antigens that are presented to T lymphocytes in association with molecules of the major histocompatibility complex. Since in a biological system T‐ and B‐cell receptors or antibody molecules face a virtual infinite number of structures, cognate interactions with epitopes are the basis of the primordial intelligence that drives the teleological choices of the immune system. Although theoretically any antigen comprises a myriad of potential epitopes, the immune response will focus only on a few of them by a phenomenon termed immunodominance. Understanding the mechanisms that govern epitope selection is important for epitope prediction and vaccine design.Key conceptsSurface immunoglobulins of B cells and antibodies recognize the B‐cell epitope of an antigen in its native conformation.The main common feature of B‐cell epitopes (BCEs) is accessibility on the surface of the antigen.T‐cell receptors (TCRs) recognize the T‐cell epitopes (TCEs) only after intracellular processing of the antigen, and in association with major histocompatibility complex (MHC) molecules, a concept termed MHC restriction.TCEs presented by MHC class II molecules are longer and more variable in size than those presented by MHC class I molecules.TCE peptides that bind to the same allele of MHC class I molecules share common ‘anchor’ residues that contact the MHC molecule. In MHC class II‐restricted TCEs, the anchor residues are less well defined.High affinity of the TCR–MHC–peptide tripartite interaction as well as coreceptors and other signalling modules are needed for T‐cell activation.Immunodominance refers to the concept that only a small subset of the potential epitopes (TCEs or BCEs) present in a given antigen elicit an immune response.The immunodominance of a TCE depends on its accessibility within the antigen, the specificity of processing enzymes and its affinity to transporter proteins, chaperons, MHC and TCRs.Mimotopes are small molecules that mimic the structure of complex conformational epitopes without any sequence homology.