Substrate-induced protein stabilization reveals a predominant contribution from mature proteins to peptides presented on MHC class I

The foundation from the MHC class I-presented peptides can be mainly from recently synthesized but defective proteins, termed defective ribosomal products. The majority of the data supporting this idea originate from studies by which inhibitors of protein synthesis put together to quickly block Ag presentation even if cells contained a swimming pool of mature proteins. However, these data only not directly address the foundation of presented peptides, as well as in most studies, the contribution of mature functional proteins towards the class I peptide pool is not directly quantified. Within this report, we address the efficiency and contribution of mature proteins utilizing a tetracycline-inducible system to convey Ags which are conditionally stabilized upon ligand binding. This technique circumvents using general inhibitors of protein synthesis to manage Ag expression. Furthermore, by controlling Ag stabilization, we’re able to investigate if the degradation of mature Ags led to Ag presentation at early and/or late time points. We reveal that Shield-1 mature proteins would be the major contributor of peptides presented on class I for 2 distinct antigenic constructs. In addition, our data reveal that the protein synthesis inhibitors used formerly to check the contribution of defective proteins really block Ag presentation with techniques which are independent from blocking Ag synthesis. These data claim that for that constructs we’ve examined, mature functional proteins, instead of defective ribosomal products, would be the predominant supply of MHC class I-presented peptides.