Immunology

Highlights

 

•T effector cell differentiation depends on de novo fatty acid (FA) synthesis.•CD8+ T memory cell development and function depend on both FA synthesis and oxidation.•FA synthesis and oxidation are determinants for CD4+ T effector versus Treg cell development.•These pathways may present therapeutic targets for modulating T cell responses in vivo.

 

The specific regulation of cellular metabolic processes is of major importance for directing immune cell differentiation and function. We review recent evidence indicating that changes in basic cellular lipid metabolism have critical effects on T cell proliferation and cell fate decisions. While induction of de novo fatty acid (FA) synthesis is essential for activation-induced proliferation and differentiation of effector T cells, FA catabolism via β-oxidation is important for the development of CD8+ T cell memory as well as for the differentiation of CD4+ regulatory T cells. We consider the influence of lipid metabolism and metabolic intermediates on the regulation of signaling and transcriptional pathways via post-translational modifications, and discuss how an improved understanding of FA metabolism may reveal strategies for manipulating immune responses towards therapeutic outcomes.

Via Krishan Maggon

Thymocytes and mature T cells are exposed to a broad range of self-peptides of varying reactivity with TCRs. Hogquist and Jameson discuss how differences in self-reactivity and TCR signal strength dictate subsequent cell fates.

 

Self-reactivity was once seen as a potential characteristic of T cells that was eliminated by clonal selection to protect the host from autoimmune pathology. It is now understood that the T cell repertoire is in fact broadly self-reactive, even self-centered. The strength with which a T cell reacts to self ligands and the environmental context in which this reaction occurs influence almost every aspect of T cell biology, from development to differentiation to effector function. Here we highlight recent advances and discoveries that relate to T cell self-reactivity, with a particular emphasis on T cell antigen receptor (TCR) signaling thresholds.

Via Krishan Maggon

Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC).

Via Krishan Maggon

How agonist peptides initiate the T cell antigen receptor (TCR) signaling cascade is widely debated. Weiss and Chakraborty discuss current models of the proximal signaling events that ensue upon recognition of agonist peptide-MHC complexes by TCRs.

 

The initiation of T cell antigen receptor signaling is a key step that can result in T cell activation and the orchestration of an adaptive immune response. Early events in T cell receptor signaling can distinguish between agonist and endogenous ligands with exquisite selectivity, and show extraordinary sensitivity to minute numbers of agonists in a sea of endogenous ligands. We review our current knowledge of models and crucial molecules that aim to provide a mechanistic explanation for these observations. Building on current understanding and a discussion of unresolved issues, we propose a molecular model for initiation of T cell receptor signaling that may serve as a useful guide for future studies.

Via Krishan Maggon