Dataset Information

Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma.

ABSTRACT: Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88^L265P, EZH2^Y641F , and EZH2^Y641N . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*02:01. Peripheral blood T cells were primed with peptide-loaded dendritic cells (DC), and reactive T cells were assessed for recognition of naturally processed mutant versus wild type full-length proteins. After screening three driver mutations across 17-26 HLA class I alleles and 3 × 10⁶-3 × 10⁷ T cells per donor, we identified CD4⁺ T cells against EFISENCGEII from EZH2^Y641N (presented by HLA-DRB1*13:02) and CD8⁺ T cells against RPIPIKYKA from MYD88^L265P (presented by HLA-B*07:02). We failed to detect RPIPIKYKA-specific T cells in seven other HLA-B*07:02-positive donors, including two lymphoma patients. Thus, healthy donors harbor T cells specific for common driver mutations in lymphoma. However, such responses appear to be rare due to the combined limitations of antigen processing, HLA restriction, and T cell repertoire size, highlighting the need for highly individualized approaches for selecting targets.

SUBMITTER: Nielsen JS

PROVIDER: S-EPMC5543822 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma.

Nielsen Julie S JS Chang Andrew R AR Wick Darin A DA Sedgwick Colin G CG Zong Zusheng Z Mungall Andrew J AJ Martin Spencer D SD Kinloch Natalie N NN Ott-Langer Susann S Brumme Zabrina L ZL Treon Steven P SP Connors Joseph M JM Gascoyne Randy D RD Webb John R JR Berry Brian R BR Morin Ryan D RD Macpherson Nicol N Nelson Brad H BH

Oncoimmunology 20170428 7

Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88L265P, EZH2Y641F , and EZH2Y641N . Donors collectively expressed the 10 ...[more]

PMID: 28811957

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Dataset Information

Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma.

Publications

Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma.

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