Agora Center, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Front Immunol. 2020 Aug 28;11:1981. doi: 10.3389/fimmu.2020.01981. eCollection 2020.
Induction of an effective tumor immunity is a complex process that includes the appropriate presentation of the tumor antigens, activation of specific T cells, and the elimination of malignant cells. Potent and efficient T cell activation is dependent on multiple factors, such as timely expression of co-stimulatory molecules, the differentiation state of professional antigen presenting cells (e.g., dendritic cells; DCs), the functionality of the antigen processing and presentation machinery (APPM), and the repertoire of HLA class I and II-bound peptides (termed immunopeptidome) presented to T cells. So far, how molecular perturbations underlying DCs maturation and differentiation affect the cross-presented HLA class I and II immunopeptidomes is largely unknown. Yet, this knowledge is crucial for further development of DC-based immunotherapy approaches. We applied a state-of-the-art sensitive MS-based immunopeptidomics approach to characterize the naturally presented HLA-I and -II immunopeptidomes eluted from autologous immune cells having distinct functional and biological states including CD14 monocytes, immature DC (ImmDC) and mature DC (MaDC) monocyte-derived DCs and naive or activated T and B cells. We revealed a presentation of significantly longer HLA peptides upon activation that is HLA allotype specific. This was apparent in the self-peptidome upon cell activation and in the context of presentation of exogenously loaded antigens, suggesting that peptide length is an important feature with potential implications on the rational design of anti-cancer vaccines.
诱导有效的肿瘤免疫是一个复杂的过程，包括适当呈现肿瘤抗原、激活特异性 T 细胞和消除恶性细胞。有效的 T 细胞激活依赖于多种因素，例如共刺激分子的及时表达、专业抗原呈递细胞（例如树突状细胞；DCs）的分化状态、抗原加工和呈递机制（APPM）的功能以及呈递给 T 细胞的 HLA 类 I 和 II 结合肽的 repertoire（称为免疫肽组）。到目前为止，DC 成熟和分化的分子扰动如何影响交叉呈递的 HLA 类 I 和 II 免疫肽组在很大程度上是未知的。然而，这些知识对于进一步开发基于 DC 的免疫治疗方法至关重要。我们应用了一种最先进的敏感 MS 免疫肽组学方法来描述从具有不同功能和生物学状态的自体免疫细胞中洗脱的天然呈递的 HLA-I 和 -II 免疫肽组，包括 CD14 单核细胞、未成熟 DC（ImmDC）和成熟 DC（MaDC）单核细胞衍生的 DC 以及幼稚或激活的 T 和 B 细胞。我们揭示了在细胞激活时呈现出明显更长的 HLA 肽，这是 HLA 同种型特异性的。这在细胞激活时的自身肽组和外源性负载抗原的呈递情况下都很明显，表明肽长度是一个重要特征，可能对癌症疫苗的合理设计有影响。
