Data from: A large fraction of HLA class I ligands are proteasome-generated spliced peptides

The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8+ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features. We validated this observation using a range of complementary experimental and bioinformatics approaches, as well as multiple cell types. The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy.

蛋白酶体（proteasome）可产生呈递于人类白细胞抗原（human leukocyte antigen, HLA）I类分子上的表位，此类表位可触发CD8阳性T细胞免疫应答。此前虽有关于蛋白酶体产生的剪接型表位的报道，但这类表位一直被视为罕见事件。然而本研究表明，从多样性维度来看，蛋白酶体产生的剪接肽库占整个HLA I类免疫肽组（immunopeptidome）的三分之一，从丰度维度来看则占四分之一。该剪接肽库同时代表一类独特的抗原集合，具备特定且鲜明的特征。研究团队通过一系列互补的实验与生物信息学方法，结合多种细胞类型对该发现进行了验证。蛋白酶体催化的肽剪接事件的广泛存在及其丰度，对免疫生物学与自身免疫理论具有重要启示，同时可为疫苗研发与癌症免疫治疗提供此前未被发掘的表位来源。