Correlation of the epitopes defined by anti-CD26 mAbs and CD26 function

Area of Science:

• Immunology
• Molecular Biology
• Biochemistry

Background:

• CD26, also known as dipeptidyl peptidase IV (DPPIV), is a cell surface glycoprotein with diverse functions in immune regulation and T-cell activation.
• Anti-CD26 monoclonal antibodies (mAbs) are crucial tools for studying CD26 function, but their correlation with specific functional outcomes remains to be fully elucidated.

Purpose of the Study:

• To delineate the specific epitopes on CD26 recognized by various anti-CD26 mAbs.
• To correlate these defined epitopes with distinct CD26 functions, including T-cell costimulation and adenosine deaminase (ADA) binding.

Main Methods:

• Utilized truncated and human-rat CD26 swap mutants to map epitopes.
• Employed cross-blocking studies to group 13 anti-CD26 mAbs into five distinct epitope groups.
• Assessed mAb avidity using dipeptidyl peptidase IV (DPPIV) enzymatic activity as an indicator.

Main Results:

• Identified five distinct epitope regions on CD26, localized to specific amino acid intervals.
• Found that mAbs targeting epitopes in the 248-358th and 359-449th regions induced CD26 modulation and T-cell costimulation via the CD3 pathway.
• Determined that the 359-449th amino acid region encompasses the ADA binding domain.
• Observed little correlation between anti-CD26 mAb avidity and CD26 function, suggesting epitope specificity is key.

Conclusions:

• Distinct epitopes on CD26 are associated with different biological functions.
• Epitope mapping of anti-CD26 mAbs provides valuable insights into the functional domains of CD26.
• These findings will aid in the development of targeted CD26-modulating therapeutics.