The T cell receptors (TCR) of conventional T cells have evolved to recognize peptide antigens presented on classical major histocompatibility complex (MHC) molecules, while innate-like αβ T cell TCRs tend to recognize non-peptide antigens presented by non-classical and non-polymorphic MHC molecules (e.g. CD1a-e, MHC-related protein 1(MR1)). The most prominent members of the innate-like αβ T cells include the lipid-reactive invariant CD1d-restricted natural killer T (iNKT) and the MR1-restricted-riboflavin metabolite recognizing mucosal-associated invariant T (MAIT) cells. NKT and MAIT cells are found across different species and collectively comprise ~1-5% of the T cell compartment in the blood of most humans and are present in the peripheral tissues. Conservation analyses reveal that species that lack functional CD1d or MR1 proteins either do not develop NKT cells or lack the invariant TRAV1 TCRα chain the majority of MAIT cells utilize, both supporting the co-evolution of these molecules. Furthermore, in the CD1 group of molecules, although five proteins CD1a-e have been identified in mammals, the number of genes that encodes these proteins varies among species. Mice only have two genes encoding for CD1d, whereas all five proteins are encoded in humans. CD1a, b, and c-restricted T cells have been identified in humans that can recognize lipid antigens from M.tuberculosis.
TCR and cytokine-mediated stimulation of innate-like T cells lead to the rapid secretion of immune-modulating cytokines which have been shown to provide immunoregulatory and effector functions towards various microbial and viral infections. Since the development and wider availability of non-classical MHC multimer reagents loaded with microbial derived metabolites and antigens, there is growing evidence that the biological function of these cells extends to autoimmune diseases, tumor immunity and other non-infectious diseases. Indeed, some CD1-restricted T cells can be activated in the presence of self-lipids, also suggesting that these autoreactive cells may also contribute pathological roles autoimmune conditions. The inflammatory activities, conservation and collective substantial frequencies in humans contribute to the utility of innate-like T cells to serve as biomarkers of disease and effector cell targets to modulate for immunotherapies. Their development across species, contributions to tissue homeostasis in non-infectious diseases warrants further investigation and is encompassed in the goal of this research topic.
This topic invites original research articles and reviews that cover but are not limited to the following areas:
1. New insights into the development of innate-like αβ T cells
2. Contributions of innate-like αβ T cells in autoimmune diseases
3. Roles innate-like αβ T cells in tumor-mediated immunity and immunopathology
4. Interplay of commensal microbiota and the modulation of innate-like αβ T cell activation
The T cell receptors (TCR) of conventional T cells have evolved to recognize peptide antigens presented on classical major histocompatibility complex (MHC) molecules, while innate-like αβ T cell TCRs tend to recognize non-peptide antigens presented by non-classical and non-polymorphic MHC molecules (e.g. CD1a-e, MHC-related protein 1(MR1)). The most prominent members of the innate-like αβ T cells include the lipid-reactive invariant CD1d-restricted natural killer T (iNKT) and the MR1-restricted-riboflavin metabolite recognizing mucosal-associated invariant T (MAIT) cells. NKT and MAIT cells are found across different species and collectively comprise ~1-5% of the T cell compartment in the blood of most humans and are present in the peripheral tissues. Conservation analyses reveal that species that lack functional CD1d or MR1 proteins either do not develop NKT cells or lack the invariant TRAV1 TCRα chain the majority of MAIT cells utilize, both supporting the co-evolution of these molecules. Furthermore, in the CD1 group of molecules, although five proteins CD1a-e have been identified in mammals, the number of genes that encodes these proteins varies among species. Mice only have two genes encoding for CD1d, whereas all five proteins are encoded in humans. CD1a, b, and c-restricted T cells have been identified in humans that can recognize lipid antigens from M.tuberculosis.
TCR and cytokine-mediated stimulation of innate-like T cells lead to the rapid secretion of immune-modulating cytokines which have been shown to provide immunoregulatory and effector functions towards various microbial and viral infections. Since the development and wider availability of non-classical MHC multimer reagents loaded with microbial derived metabolites and antigens, there is growing evidence that the biological function of these cells extends to autoimmune diseases, tumor immunity and other non-infectious diseases. Indeed, some CD1-restricted T cells can be activated in the presence of self-lipids, also suggesting that these autoreactive cells may also contribute pathological roles autoimmune conditions. The inflammatory activities, conservation and collective substantial frequencies in humans contribute to the utility of innate-like T cells to serve as biomarkers of disease and effector cell targets to modulate for immunotherapies. Their development across species, contributions to tissue homeostasis in non-infectious diseases warrants further investigation and is encompassed in the goal of this research topic.
This topic invites original research articles and reviews that cover but are not limited to the following areas:
1. New insights into the development of innate-like αβ T cells
2. Contributions of innate-like αβ T cells in autoimmune diseases
3. Roles innate-like αβ T cells in tumor-mediated immunity and immunopathology
4. Interplay of commensal microbiota and the modulation of innate-like αβ T cell activation