Linear peptides corresponding to fragment 83-98 of the first loop and fragments 168-192 and 171-182 of the second extracellular loops of M2-muscarinic receptor (marker of early cardiac disorders and arrhythmias) were synthesized by Fmoc-SPPS method. A new conformational antigen was synthesized by method of selective ligation of linear peptides by disulfide bond with native localization. Peptides were studied in reaction with sera from patients with idiopathic arrhythmias. A new conformational antigen was recognized by sera from patients with idiopathic arrhythmias with high reactivity.
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http://dx.doi.org/10.7868/s013234231303010x | DOI Listing |
Alzheimers Dement
December 2024
University of California San Francisco, San Francisco, CA, USA.
Background: The direct and chaperone-associated interactions of E3 ubiquitin ligase CHIP with tau in Alzheimer's disease and other tauopathies, regulates tau turnover, by directly linking it to ubiquitination and proteasomal degradation, as well as through suppression of tau aggregation. Modulation of these CHIP-driven tau clearance mechanisms can be an effective treatment strategy. Antigen-binding antibody fragments (Fabs) are potent tools that can highly-selectively engage target proteins and act as functional probes or inhibitors.
View Article and Find Full Text PDFFront Immunol
January 2025
Institute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Introduction: Vaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity.
View Article and Find Full Text PDFNat Commun
January 2025
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591, USA.
The T-cell receptor (TCR)/CD3 complex plays an essential role in the immune response and is a key player in cancer immunotherapies. There are two classes of TCR/CD3 complexes, defined by their TCR chain usage (αβ or γδ). Recently reported structures have revealed the organization of the αβ TCR/CD3 complex, but similar studies regarding the γδ TCR/CD3 complex have lagged behind.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
The T cell antigen presentation platform MR1 consists of 6 allomorphs in humans that differ by no more than 5 amino acids. The principal function of this highly conserved molecule involves presenting microbial metabolites to the abundant mucosal-associated invariant T (MAIT) cell subset. Recent developments suggest that the role of MR1 extends to presenting antigens from cancer cells, a function dependent on the K43 residue in the MR1 antigen binding cleft.
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