Журнал клинической и клеточной иммунологии
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Signaling Mechanisms that Balance Anti-viral, Auto-reactive, and Antitumor Potential of Low Affinity T Cells

Michael Hebeisen, Nathalie Rufer, Susanne Oberle, Daniel E Speiser and Dietmar Zehn

T cells protect us from a large number of infectious diseases. Several lines of evidence indicate that T cells can also eliminate malignant cells and alter the progression of tumors. These two types of immune responses were traditionally viewed to involve different types or qualities of T cells. Pathogen-specific immune responses were thought to be predominantly mediated by T cells bearing high affinity T cell receptors (TCRs) specific for microbial-derived antigens. In contrast, anti-tumor immunity or autoimmune diseases normally involve TCRs with intermediate-to-low affinity to self-antigens, and lower affinity T cells are believed to have severely reduced effector T cell potential. However, recent findings illustrate that the repertoire of pathogen-specific T cells is more diverse than previously considered and that significant numbers of differentiated and fully functional lower affinity effector T cells arise during infections. In this review, we will summarize our current understanding of the importance and the effector capacity of low affinity T cells during infection, autoimmunity and anti-tumor responses. We will discuss how T cell function is influenced by TCR affinity and TCR signal strength, and we will focus on how the expression of inhibitory and activating receptors impact the function of T cells with different antigen affinity. Manipulating T cell activity through engaging or blocking these pathways bears an enormous potential to alter the clinical outcome of malignant diseases, chronic infections, and autoimmune disorders.