Nature and nurture: T-cell receptor-dependent and T-cell receptor-independent differentiation cues in the selection of the memory T-cell pool

Abstract

The initiation of a T-cell response begins with the interaction of an individual T-cell clone with its cognate antigen presented by MHC. Although the strength of the T-cell receptor (TCR) -antigen-MHC (TCR-pMHC) interaction plays an important and obvious role in the recruitment of T cells into the immune response, evidence in recent years has suggested that the strength of this initial interaction can influence various other aspects of the fate of an individual T-cell clone and its daughter cells. In this review, we will describe differences in the way CD4(+) and CD8(+) T cells incorporate antigen-driven differentiation and survival signals during the response to acute infection. Furthermore, we will discuss increasing evidence that the quality and/or quantity of the initial TCR-pMHC interaction can drive the differentiation and long-term survival of T helper type 1 memory populations.

Figure 1

Hierarchical CD4⁺ T-cell differentiation is influenced by T-cell receptor avidity and antigen availability. (a) Under conditions of low antigen availability, only intermediate to high-avidity clones participate in the Th1 effector response, whereas only high-avidity clones populate the memory pool. (b) Under conditions of high antigen availability, clones with low, intermediate and high avidity participate in the effector response, whereas intermediate and high-avidity clones populate the memory pool. (c) Following repeated antigen stimulation, high-avidity clones might gain a competitive advantage and preferentially populate the effector and memory pools.