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The adaptive immune system arose around 500 million years ago in jawed fish, and, since then, it has mediated the immune defense against pathogens in all vertebrates. Antibodies play a central role in the immune reaction, recognizing and attacking external invaders. During the evolutionary process, several immunoglobulin isotypes emerged, each having a characteristic structural organization and dedicated function. In this work, we investigate the evolution of the immunoglobulin isotypes, in order to highlight the relevant features that were preserved over time and the parts that, instead, mutated. The residues that are coupled in the evolution process are often involved in intra- or interdomain interactions, meaning that they are fundamental to maintaining the immunoglobulin fold and to ensuring interactions with other domains. The explosive growth of available sequences allows us to point out the evolutionary conserved residues and compare the biophysical properties among different animal classes and isotypes. Our study offers a general overview of the evolution of immunoglobulin isotypes and advances the knowledge of their characteristic biophysical properties, as a first step in guiding protein design from evolution.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216798 | PMC |
http://dx.doi.org/10.3390/biom13050801 | DOI Listing |
Front Immunol
December 2024
Laboratory of Molecular Medicine, Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Throughout the COVID-19 pandemic, the emergence of new viral variants has challenged public health efforts, often evading antibody responses generated by infections and vaccinations. This immune escape has led to waves of breakthrough infections, raising questions about the efficacy and durability of immune protection. Here we focus on the impact of SARS-CoV-2 Delta and Omicron spike mutations on ACE-2 receptor binding, protein stability, and immune response evasion.
View Article and Find Full Text PDFMol Cell
December 2024
Drukier Institute for Children's Health, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.
View Article and Find Full Text PDFInfluenza Other Respir Viruses
December 2024
Center of Excellence in Respiratory Pathogens (CERP), Hospices Civils de Lyon (HCL), Lyon, France.
Background: Respiratory Syncytial Virus (RSV) is a major health concern, particularly for infants. In France, Nirsevimab, a long-acting monoclonal antibody to prevent RSV-associated lower respiratory tract infections (LRTI) was available from September 2023. We described RSV-associated LRTI hospitalisations during the 2023-2024 season among infants younger than six months born at the Hospices Civils de Lyon (HCL), and evaluated the effectiveness of Nirsevimab against RSV-LRTI hospitalisation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Biological Sciences, University of Denver, Denver, CO 80208.
The discovery that sponges (Porifera) can fully regenerate from aggregates of dissociated cells launched them as one of the earliest experimental models to study the evolution of cell adhesion and allorecognition in animals. This process depends on an extracellular glycoprotein complex called the Aggregation Factor (AF), which is composed of proteins thought to be unique to sponges. We used quantitative proteomics to identify additional AF components and interacting proteins in the classical model, , and compared them to proteins involved in cell interactions in Bilateria.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, United States.
The adaptive immune system generates a diverse array of B-cell receptors through the processes of V(D)J recombination and somatic hypermutation. B-cell receptors that bind to an antigen will undergo clonal expansion, creating a Darwinian evolutionary dynamic within individuals. A key step in studying these dynamics is to identify sequences derived from the same ancestral V(D)J recombination event (i.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!