T-Cell Immunopeptidomes Reveal Cell Subtype Surface Markers Derived From Intracellular Proteins.
T-Cell Immunopeptidomes Reveal Cell Subtype Surface Markers Derived From Intracellular Proteins.
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T 细胞免疫肽组揭示了源自细胞内蛋白质的细胞亚型表面标记。
DOI：
10.1002/pmic.201700410
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发表时间：
2018
期刊：
影响因子：
3.4
通讯作者：
Elias,JoshuaE
中科院分区：
文献类型：
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作者：
Olsson,Niclas;Schultz,LioraM;Zhang,Lichao;Khodadoust,MichaelS;Narayan,Rupa;Czerwinski,DebraK;Levy,Ronald;Elias,JoshuaE
免疫肽段有望成为理想的免疫治疗靶点，但其质谱（MS）表征仍然具有挑战性。直到最近，需要超过109个细胞来检测数千种HLA配体。这种有限的分析灵敏度在历史上限制了可以评价细胞培养物或散装组织的临床标本的类型。从纯化的细胞亚群中测量免疫肽段对于许多应用是优选的，特别是那些评估稀有的初级造血细胞谱系的应用。在这里，我们测试的免疫肽组分析的可行性，从有限数量的初级纯化的人调节性T细胞（TReg），传统的T细胞（Tconv），和活化的T细胞。本文报道的组合T细胞免疫肽数据集包含来自5049种蛋白质的13804个独特的HLA配体。其中，超过700种HLA配体来源于我们专门从富含TReg的细胞中鉴定的82种蛋白质。本研究1）证明了从单个供体中回收的原代、谱系富集的T细胞亚群与免疫肽组分析相容; 2）提出了新的TReg偏倚配体候选物; 3）支持免疫肽组调查揭示T细胞生物学的价值，这可能仅从表达数据中无法明显看出。总之，这些发现为靶向Treg并消除其抑制功能以治疗癌症开辟了新途径。
Immunopeptidomes promise novel surface markers as ideal immunotherapy targets, but their characterization by mass spectrometry (MS) remains challenging. Until recently, cell numbers exceeding 109were needed to survey thousands of HLA ligands. Such limited analytical sensitivity has historically constrained the types of clinical specimens that can be evaluated to cell cultures or bulk tissues. Measuring immunopeptidomes from purified cell subpopulations would be preferable for many applications, particularly those evaluating rare, primary hematopoietic cell lineages. Here, we test the feasibility of immunopeptidome profiling from limited numbers of primary purified human regulatory T cells (TReg), conventional T cells (Tconv), and activated T cells. The combined T cell immunopeptide dataset reported here contains 13 804 unique HLA ligands derived from 5049 proteins. Of these, more than 700 HLA ligands were derived from 82 proteins that we exclusively identified from TReg‐enriched cells. This study 1) demonstrates that primary, lineage‐enriched T cell subpopulations recovered from single donors are compatible with immunopeptidome analysis; 2) presents new TReg‐biased ligand candidates; and 3) supports immunopeptidome surveys' value for revealing T cell biology that may not be apparent from expression data alone. Taken together, these findings open up new avenues for targeting TRegand abrogating their suppressive functions to treat cancer.