Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The presentation of peptides by MHC class I (MHC I) molecules is crucial for adaptive immunity.
• Intracellular peptide editors, including tapasin and TAP-binding protein related (TAPBPR), regulate the MHC I peptide repertoire.
• Existing cell-free assays provide insights but may not fully reflect physiological conditions.

Purpose of the Study:

• To develop physiological systems for assessing TAPBPR-mediated peptide editing on MHC I.
• To investigate the function of membrane-associated and soluble TAPBPR in peptide exchange on cell surface MHC I.
• To explore the therapeutic potential of manipulating MHC I peptide loading.

Main Methods:

• Targeting TAPBPR to the plasma membrane to assess its function in situ.
• Utilizing exogenous soluble TAPBPR added to intact cells.
• Measuring T cell receptor engagement, IFN-γ secretion, and T cell-mediated killing following peptide loading.

Main Results:

• Membrane-associated TAPBPR effectively catalyzes peptide exchange on surface MHC I.
• Soluble TAPBPR also functions as an efficient peptide editor on surface MHC I.
• Both systems enabled the display of immunogenic peptides, leading to T cell activation and target cell killing.

Conclusions:

• Established two novel physiological systems to study TAPBPR-mediated peptide exchange on MHC class I.
• Demonstrated the ability to bypass natural antigen presentation pathways for targeted peptide loading.
• Highlighted the potential therapeutic application of TAPBPR in cancer immunotherapy by enhancing tumor immunogenicity.