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50 Years of structural immunology.
Wilson, Ian A; Stanfield, Robyn L.
  • Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA. Electronic address: wilson@scripps.edu.
  • Stanfield RL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
J Biol Chem ; 296: 100745, 2021.
Article in English | MEDLINE | ID: covidwho-1213326
ABSTRACT
Fifty years ago, the first landmark structures of antibodies heralded the dawn of structural immunology. Momentum then started to build toward understanding how antibodies could recognize the vast universe of potential antigens and how antibody-combining sites could be tailored to engage antigens with high specificity and affinity through recombination of germline genes (V, D, J) and somatic mutation. Equivalent groundbreaking structures in the cellular immune system appeared some 15 to 20 years later and illustrated how processed protein antigens in the form of peptides are presented by MHC molecules to T cell receptors. Structures of antigen receptors in the innate immune system then explained their inherent specificity for particular microbial antigens including lipids, carbohydrates, nucleic acids, small molecules, and specific proteins. These two sides of the immune system act immediately (innate) to particular microbial antigens or evolve (adaptive) to attain high specificity and affinity to a much wider range of antigens. We also include examples of other key receptors in the immune system (cytokine receptors) that regulate immunity and inflammation. Furthermore, these antigen receptors use a limited set of protein folds to accomplish their various immunological roles. The other main players are the antigens themselves. We focus on surface glycoproteins in enveloped viruses including SARS-CoV-2 that enable entry and egress into host cells and are targets for the antibody response. This review covers what we have learned over the past half century about the structural basis of the immune response to microbial pathogens and how that information can be utilized to design vaccines and therapeutics.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Receptors, Cytokine / Adaptive Immunity / SARS-CoV-2 / Immunity, Innate / Antibodies, Viral / Antigens, Viral Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: J Biol Chem Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Receptors, Cytokine / Adaptive Immunity / SARS-CoV-2 / Immunity, Innate / Antibodies, Viral / Antigens, Viral Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: J Biol Chem Year: 2021 Document Type: Article