A generalized mathematical model to estimate T- and B-cell receptor diversities using AmpliCot

Area of Science:

• Immunology
• Molecular Biology
• Bioinformatics

Background:

• Adaptive immunity relies on T- and B-cell receptor diversity generated by gene rearrangement.
• AmpliCot is a time- and cost-effective method for measuring T- and B-cell repertoire diversity.
• Previous analyses assumed linear diversity-Cot relationships based on second-order kinetics.

Purpose of the Study:

• To develop a more accurate model for interpreting AmpliCot experimental data.
• To investigate the relationship between receptor diversity and concentration × time (Cot) values.
• To propose an improved fitting procedure for analyzing T- and B-cell repertoire diversity.

Main Methods:

• Utilized a detailed kinetic model incorporating heteroduplex and transient-duplex formation.
• Applied the new model to fit experimental AmpliCot data.
• Developed and tested an alternative fitting procedure for diversity-Cot analysis.

Main Results:

• The detailed model provided significantly better fits to experimental data compared to the second-order kinetics model.
• Demonstrated nonlinear relationships between receptor diversity and Cot values.
• The proposed fitting procedure offers an improved description of Cot values and diversity.

Conclusions:

• The assumption of linear diversity-Cot relationships in AmpliCot analysis is an oversimplification.
• A more complex kinetic model accurately captures heteroduplex and transient-duplex formation.
• The novel fitting procedure enhances the interpretation of T- and B-cell repertoire diversity measurements.