RESUMEN
The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections.
Asunto(s)
Enzima Convertidora de Angiotensina 2 , Anticuerpos Monoclonales , COVID-19 , Evasión Inmune , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/química , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/genética , COVID-19/inmunología , COVID-19/virología , COVID-19/metabolismo , Sitios de Unión , Modelos Moleculares , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/metabolismo , MutaciónRESUMEN
The invariant NKT (iNKT) cells are innate-like lymphocytes that share phenotypic and functional characteristics with NK cells and T cells, playing an important role in both human and mouse physiology and disease and bridging the gap between the innate and adaptive immune responses. The frequency and subtypes of iNKT cells in major immune organs are different, which also determines the regional immune characteristics of iNKT cells. Here, we report a protocol about the isolation of iNKT cells in the thymus, spleen, and liver of C57BL/6, CD1d-/-, and Jα18-/- mice.