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Updated: Dec 30, 2025
Retroviral Transduction of T-cell Receptors in Mouse T-cells
Published on: October 22, 2010
Reverse immunology: From peptide sequence to tumor-killing human T-cell clones
Christophe Vanhaver1, Monica Gordon-Alonso2, Alexandre Bayard1
1De Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Abstract:
Recent advances in next generation sequencing expanded the availability of tumor mutanome data that list the mutations present in cancer cells. Mutated proteins are an interesting source of neoantigens that can be used to specifically target tumor cells in the context of immunotherapy. However, identifying new antigenic peptides from mutated proteins remains challenging. In this chapter, we present Reverse Immunology as an approach to identify potential antigens from any given polypeptide sequence. First, we explain the rationale behind the identification of candidate HLA-binding peptides through mass spectrometry or in silico approaches. Then, we describe the isolation of low-frequency T-cell precursors specific for the candidate peptides using peptide-HLA multimers. Finally, we discuss validation steps leading to the identification of a T-cell clone recognizing tumor cells that endogenously process the candidate peptide. We also present approaches to study the impact of the proteasome complex on candidate peptide processing.
Insights
Reverse Immunology identifies potential cancer neoantigens from tumor mutations. This approach aids immunotherapy development by pinpointing tumor-specific T-cell responses.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Next-generation sequencing provides extensive tumor mutanome data.
- Mutated proteins are a source of neoantigens for cancer immunotherapy.
- Identifying antigenic peptides from mutated proteins is a significant challenge.
Purpose of the Study:
- To present Reverse Immunology for identifying potential neoantigens from polypeptide sequences.
- To detail methods for discovering T-cell precursors specific to candidate peptides.
- To outline validation steps for identifying tumor-reactive T-cell clones.
Main Methods:
- In silico and mass spectrometry for identifying HLA-binding peptides.
- Peptide-HLA multimers for isolating low-frequency T-cell precursors.
- Proteasome complex analysis for peptide processing studies.
Main Results:
- Demonstration of Reverse Immunology as a viable strategy for neoantigen discovery.
- Successful isolation of T-cell precursors specific for candidate neoantigens.
- Identification of T-cell clones recognizing tumor cells processing specific peptides.
Conclusions:
- Reverse Immunology offers a robust framework for neoantigen identification in cancer immunotherapy.
- This approach facilitates the development of targeted immunotherapies by characterizing T-cell responses.
- Understanding peptide processing is crucial for effective neoantigen-based cancer treatments.
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