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Related Concept Videos

Genetic Screens02:46

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...

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Related Experiment Video

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A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes
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High-throughput, targeted MHC class I immunopeptidomics using a functional genetics screening platform.

Peter M Bruno1,2, Richard T Timms1,2,3, Nouran S Abdelfattah1,2

  • 1Department of Genetics, Harvard Medical School and Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA.

Nature Biotechnology
|January 2, 2023
PubMed
Summary
This summary is machine-generated.

EpiScan is a new method for identifying CD8+ T cell epitopes, accelerating the development of personalized immunotherapeutics. This technique efficiently screens large peptide libraries, improving the discovery of crucial immune targets.

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Area of Science:

  • Immunology
  • Computational Biology
  • Biotechnology

Background:

  • Identifying CD8+ T cell epitopes is crucial for developing immunotherapeutics.
  • Current methods for Major Histocompatibility Complex class I (MHC class I) ligand discovery are slow, require specialized expertise, and lack scalability for specific protein interrogation.

Purpose of the Study:

  • To present EpiScan, a novel method for large-scale MHC class I ligand discovery.
  • To improve the efficiency and scope of CD8+ T cell epitope identification for immunotherapeutic development.

Main Methods:

  • EpiScan utilizes surface MHC class I levels as a readout for peptide-MHC class I binding.
  • Oligonucleotide synthesis enables the design of large peptide pools (>100,000 peptides) for high-throughput screening.
  • EpiScan was used to analyze peptide-MHC binding, including the role of cysteine, affinity hierarchies, and viral proteomes.

Main Results:

  • EpiScan facilitates large-scale MHC class I screening by leveraging genetically encoded peptides.
  • The study revealed that cysteine increases the number of predicted MHC class I ligands by 9-21%.
  • EpiScan Predictor, developed from these data, demonstrates performance comparable to existing algorithms while accurately accounting for cysteine-containing peptides.

Conclusions:

  • EpiScan significantly accelerates CD8+ T cell epitope discovery.
  • The method enhances the prediction of MHC class I ligands, particularly those containing cysteine.
  • This advancement is vital for the development of precise, individual-specific immunotherapeutics.