Shaping the helper T cell landscape : from naive to effectors

Helper T (Th) lymphocytes play a key role in our immunity, orchestrating responses to various pathogens, vaccines, host proteins, microbiota, environmental antigens, and cancers. The development and function of Th cells depend on their T cell receptors (TCR). Each individual T cell progenitor acquires its TCR-encoding genes through stochastic genome recombination within TCRα and TCRβ loci. Collectively, TCRs of independent T cells contribute to an extremely diverse TCR repertoire. The TCR repertoire serves to recognize a large pool of distinct peptide antigens presented within major histocompatibility complexes (MHC). The interaction with MHC plays a central role in the development and function of T cells. Thus, T cell progenitors’ survival and early commitment to a Th lineage in thymus depends on MHC class II (MHC-II) recognition and the corresponding TCR signaling. Later peripheral recognition of antigens presented within MHC-II involves naive and memory Th lymphocytes in immune responses. Activated Th cells acquire specific helper phenotypes, which control the development of immune responses of an appropriate type, facilitating pathogen clearance and tissue homeostasis. Later, the exact antigen specificity and the linked Th phenotype are preserved in the form of Th memory clones, providing stable response patterns to familiar antigens. Studying the thymic and peripheral fate selection by Th cells may help to mechanically understand the successes and failures of our immune system to develop protective responses in infectious diseases, vaccinations, and cancers, as well as the generation of immune tolerance to microbiota-derived and host antigens.


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