Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens

Chruszcz, M.; Pomés, Anna; Glesner, Jill; Vailes, Lisa D.; Osinski, T.; Porebski, P.J.; Majorek, K.A.; Heymann, Peter W.; Platts-Mills, Thomas A.E.; Minor, Władek; Chapman, Martin D.

doi:10.1074/jbc.m111.311159

Cited by 79 publications

(116 citation statements)

References 57 publications

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“…In 4C1 interactions Tyr and Arg were particularly prominent, with potential contributions from hydrogen bonding, π bonding, and hydrophobic interactions. Interestingly, hydrogen-bonding networks in the binding interfaces of the 16 allergens were most frequently formed by Arg-Asp, Arg-Tyr, Asp-Arg, Asp-Tyr, Glu-Arg, Glu-Ser, and Gln-Ser pairs, distinct from a number of lysozyme-antibody complexes where Arg-Glu, Arg-Tyr, Asn-Gln, Asp-Ser, and Lys-Asp predominated [17].…”

Section: Current Perspectivesmentioning

confidence: 99%

“…Potent allergens in house dust mites include the cysteine proteases Der p 1 and Der f 1, which induce a strong response of IgE antibodies [17]. These antigens share 81 % sequence identity and elicit highly crossreactive responses.…”

Section: Current Perspectivesmentioning

confidence: 99%

“…For comparison, another antibody, Nb80, binds to the β 2 AR with a similar H-chain CDR3 β-hairpin and recognizes an active form of the receptor, whereas the β-hairpin Fab2838 CDR3 induces a different shape of binding pocket and locks the receptor in an inactive conformation [21]. Superimposed structures are based on the crystallographic data of [17]. Angles are 143° and 167° for P2 1 2 1 2 1 (blue) and C222 1 (orange) forms, respectively.…”

Section: Current Perspectivesmentioning

confidence: 99%

“…8). The authors [17] proceeded to analyse 16 available allergen-antibody complexes in the structure database and found a common theme that Tyr and Ser residues in the antibody played a dominant role in interaction with the allergen, followed by Arg, Asn, and Asp. In 4C1 interactions Tyr and Arg were particularly prominent, with potential contributions from hydrogen bonding, π bonding, and hydrophobic interactions.…”

Section: Current Perspectivesmentioning

confidence: 99%

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Structural aspects of molecular recognition in the immune system. Part I: Acquired immunity (IUPAC Technical Report)

Templeton

Moehle

2014

Pure and Applied Chemistry

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Humoral immunity allows the body to mount a defense against pathogens and foreign substances, and to respond with memory to subsequent exposures. The molecular participants may also recognize selfstructures, leading to attack on the body and autoimmune disease. The main players in humoral immunity are antibody-producing B lymphocytes, and several classes of T lymphocytes. This review deals with the molecular details of recognition of antigens by soluble antibodies, and of substances presented to receptors on the surfaces of T cells (TCRs). The prototype antibody consists of a dimer of dimers, two heavy (H) chains and two light (L) chains, with antigen recognition capacity lying in variable "head" regions of an H-L pair. Most crystallographic studies are done with this substructure, called a F ab fragment, bound in a soluble antigen complex. Homologous to this arrangement, the prototype TCR consists of two chains (α and β) that complex not soluble antigen, but usually a short peptide or other small molecule presented by proteins of the major histocompatibility complex. In each case a general background on the historical development of understanding the molecular recognition interface is given, followed by a number of examples of crystal structures from the recent literature that have allowed us to refine our understanding of the complex recognition process. Variations on the prototypical structures are also considered. The spectrum of recognition strategies involves interplay of lock-and-key with flexibility, varying degrees of entropic and enthalpic contributions, surface shaping by entrapped water molecules, and combinations of stabilizing hydrogen bonding, electrostatic interactions, salt bridging, and van der Waals forces. Preeminent in the recent literature are details of antibody binding to influenza A and human immunodeficiency viral antigens. Both viral antigens and attempts to understand autoimmunity are prominent in the recent TCR literature.

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Section: Current Perspectivesmentioning

confidence: 99%

Section: Current Perspectivesmentioning

confidence: 99%

Section: Current Perspectivesmentioning

confidence: 99%

Section: Current Perspectivesmentioning

confidence: 99%

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Structural aspects of molecular recognition in the immune system. Part I: Acquired immunity (IUPAC Technical Report)

Templeton

Moehle

2014

Pure and Applied Chemistry

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“…Based upon the success of recombinant allergens, rational design of allergenic epitopes was the next logical step, since, as far back as 1970, allergens were being chemically modified to reduce IgE binding capacity while retaining the ability to prompt the production of antigen-specific IgGs (122,123). More recently, the use of recombinant technology yielded new tools with which to mutate specific residues that alter the activity of the allergen.…”

Section: Active Allergen Immunotherapy Induces Neutralizing Antibodymentioning

confidence: 99%

Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

Karagiannis

Josephs

et al. 2013

Microbiol Spectr

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The pathogenic role of immunoglobulin E (IgE) antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Since its discovery in the 1960s, the central role of IgE in allergic disease has been intensively studied, placing IgE and its functions at the heart of therapeutic efforts for the treatment of allergies. Here, we provide an overview of the nature, roles, and significance of IgE antibodies in allergic diseases, infections, and inflammation and the utility of antibodies as therapies. We place special emphasis on allergen-IgEFcε receptor complexes in the context of allergic and inflammatory diseases and describe strategies, including monoclonal antibodies, aimed at interrupting these complexes. Of clinical significance, one antibody, omalizumab, is presently in clinical use and works by preventing formation of IgE-Fcε receptor interactions. Active immunotherapy approaches with allergens and allergen derivatives have also demonstrated clinical benefits for patients with allergic diseases. These treatments are strongly associated with serum increases of IgE-neutralizing antibodies and feature a notable redirection of humoral responses towards production of antibodies of the IgG4 subclass in patients receiving immunotherapies. Lastly, we provide a new perspective on the rise of recombinant antibodies of the IgE class recognizing tumor-associated antigens, and we discuss the potential utility of tumor antigen-specific IgE antibodies to direct potent IgE-driven immune responses against tumors.

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Food Allergens—Molecular and Immunological Characteristics

Breiteneder¹,

Mills²

2013

Food Allergy

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Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens

Cited by 79 publications

References 57 publications

Structural aspects of molecular recognition in the immune system. Part I: Acquired immunity (IUPAC Technical Report)

Structural aspects of molecular recognition in the immune system. Part I: Acquired immunity (IUPAC Technical Report)

Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

Food Allergens—Molecular and Immunological Characteristics

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