Epitopes

Claude P Muller, Institute of Immunology, Luxembourg, Luxembourg
Monique Jacoby, Institute of Immunology, Luxembourg, Luxembourg

Published online: September 2009

DOI: 10.1002/9780470015902.a0000514.pub2

T- 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 concepts

  • Surface 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.

Keywords: major histocompatibility complex; T-cell receptor; antibody; antigen; MHC restriction; paratope

Figure 1. Space-filling model of the interaction of a 7-mer peptide (dark red) of the antigen with the paratope of the antibody Fab fragment. The complementarity determining regions (CDRs) forming the paratope are shown in different colours. The hypervariable loops H1 (cyan), H2 (pale magenta), H3 (yellow), L1 (dark blue) and L3 (green) contact the peptide, while L2 (magenta) does not interact with the peptide. Reproduced from Stanfield RL, Fieser TM, Lerner RA and Wilson IA (1990) Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 A. Science 248: 712–719. Copyright © 1990 American Association for the Advancement of Science.
Figure 2. (a) Recognition of lysozyme (green) by the hypervariable regions of the heavy (blue) and light chain (yellow) of the Fab fragment of antibody D1.3. Glu121 (red) is an important residue in the centre of the epitope which interacts with both the heavy and the light chain of the paratope. (b) Antibody and antigen were separated to show the complementarity of their interacting surfaces. (c) After a 90 °C rotation the two molecules show the antibody–antigen interface, with the contact residues in red. Reproduced from Amit AG, Mariuzza RA, Philips SE and Poljak RJ (1986) Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science 233: 747–753. Copyright © 1990 American Association for the Advancement of Science.
Figure 3. Ribbon diagrams (a,b) and space filling models (c,d) of the binding groove of MHC class I and class II molecules. In MHC class I molecules (a,c), the whole peptide, including its ends, are buried within the peptide groove. In MHC class II molecules (b,d), the groove is open on both ends allowing the C- and N-terminal ends of longer peptides to protrude. In (c) and (d), the positive and negative electrostatic potential of the MHC molecule is shown in blue and red. Reproduced by permission from Murphy KM, Travers P and Walport M (2007) Janeway's Immunobiology. New York: Garland Science Publishing. Copyright holder Garland Science/Taylor & Francis LLC.
Figure 4. TCR recognition of the peptide–MHC complex. Analysis of several TCR–MHC–peptide complexes showed a similar orientation of the TCR on top of the peptide–MHC complex. The CDRs of the T-cell receptor are colour coded: the CDR1 and CDR2 loops of the chain in light and dark blue, the CDR1 and CDR2 loops of the chain in light and dark purple, the chain CDR3 loop in yellow and the chain CDR3 loop in green, the chain HV4 loop in red. The thick yellow line P1–P8 is the MHC-bound peptide. Reproduced by permission from Murphy KM, Travers P and Walport M (2007) Janeway's Immunobiology. New York: Garland Science Publishing. Copyright holder I.A. Wilson.
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    Godfrey DI, Rossjohn J and McCluskey J (2008) The fidelity, occasional promiscuity, and versatility of T-cell receptor recognition. Immunity 28: 304–314.
    Held W and Mariuzza RA (2008) Cis interactions of immunoreceptors with MHC and non-MHC ligands. Nature Reviews Immunology 8: 269–278.
    Peters B and Sette A (2007) Integrating epitope data into the emerging web of biomedical knowledge resources. Nature Reviews Immunology 7: 485–490.

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Cells of the Immune System | Antigens
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Article Title: Epitopes
 
How to Cite close
Muller, Claude P, and Jacoby, Monique(Sep 2009) Epitopes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000514.pub2]