HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy.
HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy.
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DOI：
10.1136/jitc-2020-002071
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发表时间：
2021-04
影响因子：
10.9
通讯作者：
Neidert MC
中科院分区：
文献类型：
--
作者：
Marcu A;Bichmann L;Kuchenbecker L;Kowalewski DJ;Freudenmann LK;Backert L;Mühlenbruch L;Szolek A;Lübke M;Wagner P;Engler T;Matovina S;Wang J;Hauri-Hohl M;Martin R;Kapolou K;Walz JS;Velz J;Moch H;Regli L;Silginer M;Weller M;Löffler MW;Erhard F;Schlosser A;Kohlbacher O;Stevanović S;Rammensee HG;Neidert MC
人白细胞抗原（HLA）复合物通过向免疫细胞呈递细胞内和细胞外蛋白质含量的确定部分来控制适应性免疫。了解良性HLA配体库是确定安全的基于T细胞的抗癌免疫疗法的先决条件。由于良性组织的可用性差，如果可用的话，在定义肿瘤相关抗原时，邻近肿瘤的正常组织已被用作良性替代物。然而，这种比较已被证明是不够的，甚至导致致命的结果。为了将肿瘤免疫肽组与等效对应物相匹配，我们创建了HLA配体图谱，这是第一个从227个良性人体组织样本中广泛收集配对的HLA-I和HLA-II免疫肽组的图谱。该数据集有助于肿瘤和良性组织之间在HLA配体水平上的平衡比较。尸检时从16名受试者中获得人体组织样本，5份胸腺样本和2份卵巢样本来自活体供体。通过免疫亲和纯化分离HLA配体，并在超过1200次液相色谱质谱运行中进行分析。采用实验和计算可重复的协议进行数据采集和处理。首次发布涵盖51种HLA-I和86种HLA-II同种异型，提供90，428种HLA-I配体和142，625种HLA-II配体。HLA同种异型是世界人口的代表。我们观察到免疫肽组在组织和个体之间在源蛋白和HLA配体水平上有很大差异。此外，我们发现1407 HLA-I配体从非典型的基因组区域。此类肽先前在肿瘤、外周血单核细胞（PBMC）、健康肺组织和细胞系中描述。在胶质母细胞瘤的病例研究中，我们表明，通过将肿瘤免疫肽段与所提供的多组织参考进行比较，可以避免免疫治疗中潜在的靶向脱靶肿瘤不良事件。鉴于基于T细胞的免疫疗法，如CAR-T细胞，亲和力增强的T细胞转移，癌症疫苗和免疫检查点抑制具有显著的副作用，HLA配体图谱是定义具有改善的安全性的肿瘤相关靶点的第一步。该资源提供了对癌症免疫治疗，感染，移植，过敏和自身免疫背景下的基本和应用免疫相关问题的见解。它是公开的，可以在https://hla-ligand-atlas.org的易于使用的Web界面中浏览。
The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level. Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing. The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference. Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at https://hla-ligand-atlas.org.
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影响因子：
64.8
作者：
Kim, Min-Sik;Pinto, Sneha M.;Getnet, Derese;Nirujogi, Raja Sekhar;Manda, Srikanth S.;Chaerkady, Raghothama;Madugundu, Anil K.;Kelkar, Dhanashree S.;Isserlin, Ruth;Jain, Shobhit;Thomas, Joji K.;Muthusamy, Babylakshmi;Leal-Rojas, Pamela;Kumar, Praveen;Sahasrabuddhe, Nandini A.;Balakrishnan, Lavanya;Advani, Jayshree;George, Bijesh;Renuse, Santosh;Selvan, Lakshmi Dhevi N.;Patil, Arun H.;Nanjappa, Vishalakshi;Radhakrishnan, Aneesha;Prasad, Samarjeet;Subbannayya, Tejaswini;Raju, Rajesh;Kumar, Manish;Sreenivasamurthy, Sreelakshmi K.;Marimuthu, Arivusudar;Sathe, Gajanan J.;Chavan, Sandip;Datta, Keshava K.;Subbannayya, Yashwanth;Sahu, Apeksha;Yelamanchi, Soujanya D.;Jayaram, Savita;Rajagopalan, Pavithra;Sharma, Jyoti;Murthy, Krishna R.;Syed, Nazia;Goel, Renu;Khan, Aafaque A.;Ahmad, Sartaj;Dey, Gourav;Mudgal, Keshav;Chatterjee, Aditi;Huang, Tai-Chung;Zhong, Jun;Wu, Xinyan;Shaw, Patrick G.;Freed, Donald;Zahari, Muhammad S.;Mukherjee, Kanchan K.;Shankar, Subramanian;Mahadevan, Anita;Lam, Henry;Mitchell, Christopher J.;Shankar, Susarla Krishna;Satishchandra, Parthasarathy;Schroeder, John T.;Sirdeshmukh, Ravi;Maitra, Anirban;Leach, Steven D.;Drake, Charles G.;Halushka, Marc K.;Prasad, T. S. Keshava;Hruban, Ralph H.;Kerr, Candace L.;Bader, Gary D.;Iacobuzio-Donahue, Christine A.;Gowda, Harsha;Pandey, Akhilesh
通讯作者：
Pandey, Akhilesh
DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
MHC I类的性质提出了增强免疫原性的肽。
影响因子：
4.3
作者：
Calis JJ;Maybeno M;Greenbaum JA;Weiskopf D;De Silva AD;Sette A;Keşmir C;Peters B
通讯作者：
Peters B
影响因子：
64.5
作者：
Jiang L;Wang M;Lin S;Jian R;Li X;Chan J;Dong G;Fang H;Robinson AE;GTEx Consortium;Snyder MP
通讯作者：
Snyder MP
影响因子：
16.6
作者：
Aran D;Camarda R;Odegaard J;Paik H;Oskotsky B;Krings G;Goga A;Sirota M;Butte AJ
通讯作者：
Butte AJ