Multi-level Strategy for Identifying Proteasome-Catalyzed Spliced Epitopes Targeted by CD8⁺ T Cells during Bacterial...

Area of Science:

• Immunology
• Molecular Biology
• Proteasome Biology

Background:

• Proteasome-catalyzed peptide splicing (PCPS) generates peptides for MHC class I presentation.
• The immunological significance of spliced peptides remains largely unexplored due to identification challenges.

Purpose of the Study:

• To develop and apply a novel multi-level approach for identifying proteasome-generated spliced epitopes.
• To investigate the role of spliced epitopes in the immune response to Listeria monocytogenes infection.

Main Methods:

• Utilized a reverse immunology-based multi-level strategy.
• Applied the strategy to a murine model of Listeria monocytogenes infection.
• Identified spliced epitopes within the bacterial phospholipase PlcB.

Main Results:

• Two spliced epitopes derived from bacterial PlcB were identified in L. monocytogenes-infected mice.
• These spliced epitopes primed antigen-specific CD8+ T cells.
• CD8+ T cells recognized spliced epitopes but not non-spliced peptide fragments within their natural sequences.

Conclusions:

• PCPS expands the CD8+ T cell response against L. monocytogenes by presenting spliced epitopes.
• The developed multi-level strategy enables systematic identification of spliced epitopes.
• Findings offer new avenues for immunotherapy and vaccine design targeting spliced epitopes.