Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation

TLDR

T‑cell receptor recognition of antigen is the essential first step in initiating a T‑cell response, and understanding CD4 T‑cell differentiation rules is key for effective vaccine design. CD4 T cells distinguish antigen affinity from dose, producing distinct effector and memory subsets, and memory cells retain a bias toward the strength of the initial activation that is not overridden by higher antigen dose.

Abstract

Significance T-cell receptor recognition of antigen is an essential first step in the initiation of a T-cell response. This report demonstrates that CD4 T cells responding during an infection can discriminate between antigen affinity and antigen dose, resulting in distinct types of effector and memory cell generation. Moreover, memory T cells “remember” the strength of primary T-cell activation and maintain a biased recall response upon secondary infection. These data reveal that antigen affinity exerts an important influence on T-cell differentiation that is not compensated for by high antigen dose. Understanding the rules of CD4 T-cell differentiation is integral to effective vaccine design.