Journal article

Understanding CD8( ) T-cell responses toward the native and alternate HLA-A*02:01-restricted WT1 epitope

Thi HO Nguyen, Amabel CL Tan, Sue D Xiang, Anne Goubier, Kim L Harland, E Bridie Clemens, Magdalena Plebanski, Katherine Kedzierska

CLINICAL & TRANSLATIONAL IMMUNOLOGY | WILEY | Published : 2017

Abstract

The Wilms' tumor 1 (WT1) antigen is expressed in solid and hematological malignancies, but not healthy tissues, making it a promising target for cancer immunotherapies. Immunodominant WT1 epitopes, the native HLA-A2/WT1126-134 (RMFPNAPYL) (HLA-A2/RMFPNAPYL epitope (WT1A)) and its modified variant YMFPNAPYL (HLA-A2/YMFPNAPYL epitope (WT1B)), can induce WT1-specific CD8+ T cells, although WT1B is more stably bound to HLA-A*02:01. Here, to further determine the benefits of those two targets, we assessed the naive precursor frequencies; immunogenicity and cross-reactivity of CD8+ T cells directed toward these two WT1 epitopes. Ex vivo naive WT1A- and WT1B-specific CD8+ T cells were detected in h..

View full abstract

Grants

Awarded by Australian National Health and Medical Research Council (NHMRC) Program


Funding Acknowledgements

HLA-A2.1 transgenic HHD mice were developed by Dr Francois Lemonnier (Pasteur Institute, Paris, France). We thank Matthew Caverley and Paul Thomas for their technical expertise in TCR sequence analysis. This work was supported by PX Biosolutions and by the Australian National Health and Medical Research Council (NHMRC) Program Grant (ID 1071916). KK and MP are supported by the NHMRC Senior Research Fellowships. EBC is supported by the NHMRC Peter Doherty Fellowship.