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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Epitope identification for p53R273C mutant
Jian Zhang1,2,3, Minglu Liu2, Yin Chen3
1School of Medicine, Nankai University, Tianjin, China.
Background:
With the rise of immunotherapy based on cancer neoantigen, identification of neoepitopes has become an urgent problem to be solved. The TP53 R273C mutation is one of the hotspot mutations of TP53, however, the immunogenicity of this mutation is not yet clear. The aim of this study is to identify potential epitopes for p53R273C mutant.
Methods:
In this study, bioinformatic methods, peptide exchange assay, and peptide-immunized human leukocyte antigen (HLA) transgenic mouse model were used to explore the immunogenicity of this mutation.
Results:
Peptides with higher affinity to common HLA-A alleles (A*11:01, A*02:01) were discovered by computational prediction. All the 8-11 mer peptides contain the mutation site were synthesized and soluble peptides were used in the peptide exchange assay. However, the exchange efficiencies of these predicted peptides to HLAs were lower. Fortunately, other peptides with higher exchange efficiency were discovered. Then, the immunogenicity of these peptides was validated with the HLA-A2 transgenic mice model.
Conclusion:
We identified three potential neoepitopes of p53R273C for HLA-A*02:01, one potential neoepitope for HLA-A*11:01 and no neoepitope for HLA-A*24:02.
Insights
This study identifies potential neoepitopes from the TP53 R273C mutation, crucial for developing cancer neoantigen immunotherapies. Researchers found specific neoepitopes for HLA-A*02:01 and HLA-A*11:01 alleles.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Neoantigen identification is critical for cancer immunotherapy development.
- The immunogenicity of the TP53 R273C mutation, a common TP53 hotspot, remains unclear.
- This study aims to identify potential neoepitopes arising from the p53R273C mutation.
Purpose of the Study:
- To identify potential neoepitopes derived from the TP53 R273C mutation.
- To assess the immunogenicity of these potential neoepitopes.
- To aid in the development of personalized cancer immunotherapies.
Main Methods:
- Bioinformatic prediction of peptides with high affinity to common HLA-A alleles (A*11:01, A*02:01).
- Peptide synthesis and validation using peptide exchange assays.
- Immunogenicity assessment in a human leukocyte antigen (HLA)-A2 transgenic mouse model.
Main Results:
- Computational prediction identified peptides with high affinity to HLA-A*11:01 and HLA-A*02:01.
- Peptide exchange assays revealed peptides with higher exchange efficiency.
- Validation in HLA-A2 transgenic mice confirmed immunogenicity of selected peptides.
- Identified three potential neoepitopes for HLA-A*02:01 and one for HLA-A*11:01.
Conclusions:
- Three potential neoepitopes for p53R273C were identified for HLA-A*02:01.
- One potential neoepitope for p53R273C was identified for HLA-A*11:01.
- No neoepitopes were identified for HLA-A*24:02, suggesting allele-specific presentation.
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