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Position-Scanning Peptide Libraries as Particle Immunogens for Improving CD8+ T-Cell Responses
Xuedan He1, Shiqi Zhou1, Breandan Quinn1
1University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|October 30, 2021
Summary
Position-scanning peptide libraries displayed on nanoliposomes enhance CD8+ T cell responses against MHC-I epitopes. This approach improves immunogenicity for potential therapeutic applications.
Area of Science:
- Immunology
- Vaccinology
- Molecular Biology
Background:
- Short peptides representing Major Histocompatibility Complex (MHC) class I (MHC-I) epitopes often exhibit inadequate immunogenicity for potent antigen (Ag)-specific CD8+ T cell induction.
- Developing strategies to enhance T cell responses against endogenous MHC-I epitopes is crucial for effective immunotherapy.
Purpose of the Study:
- To investigate the potential of position-scanning peptide libraries as improved immunogens for inducing robust Ag-specific CD8+ T cell responses.
- To evaluate the efficacy of nanoliposome-displayed peptide libraries in enhancing T cell immunity against viral and tumor-associated MHC-I epitopes.
Main Methods:
- Construction and display of position-scanning peptide libraries on immunogenic nanoliposomes, with single randomized positions within MHC-I epitopes.
- Assessment of library-induced Ag-specific CD8+ T cell frequency, function, and repertoire diversity.
- Comparison of library performance against wild-type epitopes and established single mutation mimotopes, including evaluation of antitumor efficacy.
Main Results:
- A position-scanning library randomized at amino acid position 5 (Pos5) enhanced CD8+ T cell responses for one tested MHC-I epitope from murine leukemia virus (MuLV) gp70.
- For a second gp70 MHC-I epitope, multiple positional libraries (Pos1, Pos3, Pos5, Pos8) and a library mixture significantly boosted CD8+ T cell responses.
- The Pos1-3-5-8 library mixture generated a more diverse epitope-specific T cell repertoire and demonstrated superior antitumor efficacy compared to a single mutation mimotope.
Conclusions:
- Position-scanning peptide libraries, when presented on nanoliposomes, can function as effective immunogens to enhance CD8+ T cell responses.
- This strategy offers a promising approach for improving T cell-mediated immunity against endogenously expressed MHC-I epitopes for therapeutic benefit.
