A loop structure allows TAPBPR to exert its dual function as MHC I chaperone and peptide editor

Area of Science:

• Immunology
• Molecular Biology
• Protein Structure-Function Relationships

Background:

• Adaptive immunity relies on Major Histocompatibility Complex class I (MHC I) molecules presenting peptides.
• Peptide loading onto MHC I is a selective process known as peptide editing, crucial for immune response.
• Tapasin and TAPBPR are key chaperones catalyzing peptide editing, with TAPBPR's 'scoop loop' function being poorly understood.

Purpose of the Study:

• To elucidate the precise function of the TAPBPR scoop loop in peptide editing.
• To investigate the role of the scoop loop in MHC I-chaperone complex stability and peptide exchange dynamics.

Main Methods:

• Utilized a reconstituted system with defined peptide-exchange components.
• Employed human TAPBPR variants to study the scoop loop's contribution.
• Analyzed the impact of the scoop loop on MHC I stability and peptide binding.

Main Results:

• Demonstrated a significant role for the TAPBPR scoop loop in stabilizing the MHC I-chaperone complex.
• Revealed that the scoop loop functions as an internal peptide surrogate, particularly in peptide-depleted conditions.
• Showed that the scoop loop stabilizes empty MHC I and prevents premature peptide rebinding, acting as a selectivity filter.

Conclusions:

• The TAPBPR scoop loop is critical for MHC I stability and effective peptide editing.
• This structural feature acts as an internal peptide surrogate, enhancing the selectivity of peptide loading.
• The scoop loop contributes to shaping the repertoire of presented epitopes, influencing the hierarchy of immune responses.