Three dimensional structure directs T-cell epitope dominance associated with allergy

<p>Abstract</p> <p>Background</p> <p>CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens.</p> <p>Methods</p> <p>The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy.</p> <p>Results</p> <p>Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen.</p> <p>Conclusion</p> <p>During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.</p

Structural Analysis of Spike Protein Mutations in the SARS-CoV-2 P.3 Variant

ABSTRACTA SARS-CoV-2 lineage designated as P.3 with multiple signature mutations in the Spike protein region was recently reported with cases from the Central Visayas Region of the Philippines. Whole genome sequencing revealed that the 33 samples under this lineage all contain the E484K, N501Y, and P681H Spike mutations previously found in variants of concern (VOC) such as the B.1.351, the P.1 and B.1.1.7 variants first reported in South Africa, Brazil, and the United Kingdom, respectively. The possible implications of the mutations found in the Spike protein of P.3 were analyzed for their potential effects on structure, stability, and molecular surface character. The analysis suggests that these mutations could significantly impact the possible interactions of the Spike protein with the ACE2 receptor and neutralizing antibodies, and warrants further clinical investigation. Some of the mutations affecting the N and C terminal domains may have effects on Spike monomer and trimer stability. This report provides insights on relevant targets for the design of future diagnostics, therapeutics and vaccines against the evolving SARS-CoV-2 variants in the Philippines.</jats:p