CD4 T Cell Affinity Diversity Is Equally Maintained during Acute and Chronic Infection

Area of Science:

• Immunology
• Infectious Diseases
• T cell biology

Background:

• T cell receptor (TCR) affinity for peptide-MHC complexes is crucial for T cell function, differentiation, and memory formation.
• The impact of chronic infections on the overall profile of TCR affinity for antigens (Ag) remains poorly understood.
• Investigating TCR affinity differences between acute and chronic infections is essential for understanding immune responses.

Purpose of the Study:

• To compare the TCR affinity profile of CD4 T cells during acute versus chronic lymphocytic choriomeningitis virus (LCMV) infection.
• To determine if chronic antigen exposure skews TCR affinity in T cells.
• To evaluate the correlation between direct TCR affinity measurements and indirect avidity assays.

Main Methods:

• Utilized the two-dimensional micropipette adhesion frequency assay for comprehensive TCR affinity analysis.
• Employed MHC class II tetramer and functional avidity assays as indirect affinity evaluation methods.
• Tracked IA^b GP_61-80-specific CD4 T cells in mouse models of acute (Armstrong) and chronic (clone 13) LCMV infection.

Main Results:

• CD4 T cell population affinity peaked during the effector phase and declined with memory formation in both acute and chronic infections.
• The range and average relative two-dimensional TCR affinity were equivalent between acute and chronic infections.
• Functional avidity and tetramer avidity measurements showed divergent results and lacked consistent correlation with direct TCR affinity.

Conclusions:

• Chronic antigen stimulation does not skew the intrinsic TCR affinity repertoire of T cells.
• The immune system maintains a diverse range of TCR affinities even under sustained antigenic pressure.
• Discrepancies between direct TCR affinity and indirect avidity assays highlight the complexity of T cell activation.