Asunto(s)
Autoanticuerpos/biosíntesis , Plaquetas/efectos de los fármacos , Exenatida/efectos adversos , Hipoglucemiantes/efectos adversos , Trombocitopenia/inducido químicamente , Plaquetas/inmunología , Plaquetas/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Exenatida/inmunología , Humanos , Hipoglucemiantes/inmunología , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Receptores Fc/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Rituximab/uso terapéutico , Trombocitopenia/diagnóstico , Trombocitopenia/inmunología , Trombopoyetina/uso terapéuticoAsunto(s)
Antibacterianos/efectos adversos , Autoanticuerpos/biosíntesis , Plaquetas/efectos de los fármacos , Trombocitopenia/inducido químicamente , Antibacterianos/inmunología , Plaquetas/inmunología , Plaquetas/patología , Dexametasona/efectos adversos , Dexametasona/inmunología , Exenatida/efectos adversos , Exenatida/inmunología , Flavonoides/efectos adversos , Flavonoides/inmunología , Humanos , Vacunas contra la Influenza/efectos adversos , Tacrolimus/efectos adversos , Tacrolimus/inmunología , Trombocitopenia/diagnóstico , Trombocitopenia/inmunología , Trimetoprim/efectos adversos , Trimetoprim/inmunologíaRESUMEN
Immunogenicity is a major concern in drug development as anti-drug antibodies in many cases affect both patient safety and drug efficacy. Another concern is often the limited half-life of drugs, which can be altered by different chemical modifications, like acylation with fatty acids. However, acylation with fatty acids has been shown in some cases to modulate T cell activation. Therefore, to understand the role of acylation with fatty acids on immunogenicity we tested three immunogenic non-acylated peptides and 14 of their acylated analogues for binding to 26 common HLA class II alleles, and their ability to activate T cells in an ex vivo T cell assay. Changes in binding affinity associated with acylation with fatty acids were typically modest, though a significant decrease was observed for influenza HA acylated with a stearic acid, and affinities for DQ alleles were consistently increased. Importantly, we showed that for all three immunogenic peptides acylation with fatty acids decreased their capacity to activate T cells, a trend particularly evident with longer fatty acids typically positioned within the peptide HLA class II binding core region, or when closer to the C-terminus. With these results we have demonstrated that acylation with fatty acids of immunogenic peptides can lower their stimulatory capacity, which could be important knowledge for drug design and immunogenicity mitigation.