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Immunoglobulins
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
If the antibody paratope in isolation may be said to have a function, it is its specific interaction with a complementary epitope. The combining site-antigen interaction is determined by spatial arrangements of chemical functional groups, much as are the interactions of enzymes with their substrates. Four types of physicochemical interactions occur between paratopes and epitopes. Van der Waal’s forces, or induced dipole interactions are extremely short-range attractions occurring between atoms without permanent dipole moments. Hydrogen bonds are highly directional forces occurring when hydrogen atoms are interposed between two electronegative atoms such as oxygen (Figure 4–15). Electrostatic forces are important when functional groups in the combining site and on the antigen bear electric charges or permanent dipole moments. In these instances, the strength of the interaction may depend on pH. So-called hydrophobic interactions refer to the increased entropy resulting when water is excluded from regions of the antibody-antigen interface containing aliphatic or aromatic residues. This is the same principle by which “oil and water don’t mix.” Examples of these chemical interactions are shown in Figure 4–16.
Antigen-antibody reactions
Published in Gabriel Virella, Medical Immunology, 2019
The reaction between antigens and antibodies involves complementary binding sites on the antibody and on the antigen molecules. The antigen molecules usually have numerous epitopes sites that combine with the binding site (paratope) of an antibody. In the same way that the binding site is determined by different segments on the variable regions of heavy and light chains that come in close proximity due to the folding of those regions, the epitopes are also formed by discontinuous segments of an antigen molecule. Some subsets of amino acids within the epitope contribute most of the binding energy with the antibody, while the surrounding residues provide structural complementary, which may play a stabilizing role when antigens and antibodies interact.
Definition of an Allergen (Immunobiology)
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2014
Malcolm N. Blumenthal, Lauren Fine
Normally, antigen recognition by both T- and B cells is required for elicitation of humoral immunity. B-cell recognition and specific antibody response is directed toward a unique surface region of the antigen. B-cell epitopes are conformational and generally have a surface area of 500–1000 Å2 [5,6]. The antibody’s antigen-binding region, composed jointly by variable regions of the light and heavy chains, is called the “paratope” and forms a tightly fitting complementary surface with the antigen’s B-cell epitope. The juxtapositioning of charges and hydrophobic mountains or valleys within epitope and paratope produces the free energy for the binding reaction. The precise fit of the two surfaces excludes most of the hydration water, tightening the complex [7]. The surface of an antigen represents a quilt of putative epitopes although how many of those putative epitopes dominate the antibody response varies from case to case [8]. Because the antibody is directed toward a specific epitope, either linear or conformational, that antibody will recognize another antigen if it carries the same or a very similar epitope. This is the basis for observed cross-reactivity between antigens [9]. To date, the prediction of allergen cross-reactivity has mainly been based on protein homology (i.e., linear sequence data). The structure and position of dominating epitopes are being described for an increasing number of protein antigens [5].
Recent trends in next generation immunoinformatics harnessed for universal coronavirus vaccine design
Published in Pathogens and Global Health, 2023
Chin Peng Lim, Boon Hui Kok, Hui Ting Lim, Candy Chuah, Badarulhisam Abdul Rahman, Abu Bakar Abdul Majeed, Michelle Wykes, Chiuan Herng Leow, Chiuan Yee Leow
An epitope is the part of an antigen that is recognized by the adaptive immune system. It binds to specific receptors including antibodies, MHC molecules and T-cell receptors [28]. The binding portion of an antibody is termed a paratope. Epitopes can be either continuous or discontinuous. A continuous or linear epitope is a relatively short (usually 5–6) amino acid sequences recognized by the paratope of a corresponding antibody. In contrast, a discontinuous epitope consists of non-adjacent segments of amino acids, not necessarily from one chain, which form a specific 3D structure, which can also be recognized by antibodies. Since discontinuous epitope arises from a specific 3D fold, it is also known as conformational epitope. Notably, epitopes recognized by B-cell epitopes may contain lipids, nucleic acids or carbohydrates, giving resultant antibodies a vast repertoire while T-cell epitopes are usually peptide fragments. The investigation, identification and development of epitopes are crucial in promoting the advancement of diagnostics and therapeutics [110].
Current strategies for detecting functional convergence across B-cell receptor repertoires
Published in mAbs, 2021
Matthew I. J. Raybould, Anthony R. Rees, Charlotte M. Deane
Rather than imposing a sequence identity restriction across the whole CDRH3 loop, paratyping33 seeks to differentiate between CDR loop residues whose identity can vary without consequence and those whose identity is crucial for same-epitope complementarity. This builds on recent improvements in epitope-agnostic paratope prediction, to the point where heavy chain (VH) paratope residues can now be predicted with a Receiver Operating Characteristic Area Under the Curve (ROC AUC) of over 87%.106 Paratyping clusters over those antibody residues predicted to be in the paratope using a threshold of 75% sequence identity. While paratyping is sequence-based like clonotyping, some general features of antibody structure may be captured due to the use of predicted paratope residues. Experimental validation on antigen-sorted and bulk BCR-seq data from repertoires responding to pertussis toxoid demonstrated that paratyping can successfully identify a higher proportion of antigen-complementary VH sequences than clonotyping.33
Understanding the human antibody repertoire
Published in mAbs, 2020
An explanation of how paratope specificity is encoded may be beginning to emerge from analyses such as the recent work of Akbar et al.,73 whose mammoth study on 825 antibody-protein antigen complexes from 84 different antigen classes attempted to define shared paratope ‘motifs’ based on interaction surfaces involving different CDR and framework residues. The motifs derived from the data set did not cluster by antigen class but were shared across antigen classes. Further, the antigen and antibody sequences (and antibody germline V-genes) differed substantially across the different complexes. This analysis resulted in fewer than 104 interaction motifs, which the authors propose represents a substantial (50%) portion of the global paratope interaction space. This ‘structural’ space would then be more than 10 orders of magnitude smaller than the postulated global antibody sequence space. While the estimate of 104 motifs is surprisingly low, the concept aligns with Perelsen’s notion that a limited number of paratope structural motifs that is also many orders of magnitude lower than the theoretical number of sequences, can provide an interaction surface repertoire for all antigens. It also reinforces the view of D’Angelo et al.72 that the contribution of a number of different CDRs (and perhaps indirectly, framework sequences) to antigen specificity is essential, notwithstanding the likelihood that CDRH3 is a critical contributor.