Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma.
Oncoimmunology
; 6(7): e1321184, 2017.
Article
en En
| MEDLINE
| ID: mdl-28811957
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 MYD88L265P, EZH2Y641F , and EZH2Y641N . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*0201. 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 EZH2Y641N (presented by HLA-DRB1*1302) and CD8+ T cells against RPIPIKYKA from MYD88L265P (presented by HLA-B*0702). We failed to detect RPIPIKYKA-specific T cells in seven other HLA-B*0702-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.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Oncoimmunology
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá