[HTML][HTML] CD1, MR1, NKT, and MAIT: evolution and origins of non-peptidic antigen recognition by T lymphocytes

DM Zajonc, MF Flajnik - Immunogenetics, 2016 - Springer
Immunogenetics, 2016Springer
T cell-mediated immunity against infection and tumors is a central feature of the adaptive
immune system. Identifying antigens that induce T cell activation, and understanding the
mechanism of antigen recognition and subsequent activation, are crucial for developing
therapeutic strategies aimed at modulating T cell responses. While peptides presented by
the polymorphic major histocompatibility complex (MHC) class I and II antigen-presenting
molecules provide the majority of antigens recognized by alpha/beta TCR-bearing T cells …
T cell-mediated immunity against infection and tumors is a central feature of the adaptive immune system. Identifying antigens that induce T cell activation, and understanding the mechanism of antigen recognition and subsequent activation, are crucial for developing therapeutic strategies aimed at modulating T cell responses. While peptides presented by the polymorphic major histocompatibility complex (MHC) class I and II antigen-presenting molecules provide the majority of antigens recognized by alpha/beta TCR-bearing T cells, other chemical classes of antigens have been identified in the past 20 years that are presented mainly to Binnate T cells.^ These antigens include lipids and glycolipids presented by the CD1 family, and, more recently, microbial vitamin B metabolites presented by MR1. T cells restricted by these class I molecules often show innate-like and unique characteristics, such as either having a conserved TCR rearrangement (semi-invariant type I NKT cells and MAIT cells), a restricted T cell repertoire (CD1b-restricted GEM T cells), or a mode of T cell activation that is independent of direct antigen contacts (CD1aautoreactive T cells). Like innate lymphoid cells (ILC), NK cells, and certain memory T cells subsets, type I NKT cells can also be exclusively activated by cytokine stimulation without any TCR activation. This issue will touch on all of these aforementioned structural and functional characteristics of innate T cells, focusing on CD1-and MR1-restricted T cells but also touching on non-classical MHC class I (MHC Ib)-restricted T cells for which the presented antigen is unknown. This special issue begins with the discovery and evolution of the antigen presenting molecules MR1 and CD1, and then shifts to the structural and biochemical characterization of the interaction between these non-classical class I antigen-presenting molecules and the semi-invariant TCR. Studies of innate T cell activation are tackled next, followed by a discussion of potential therapeutic applications of type I NKT cells, their role in infection and cancer, and the immune regulatory properties of type II NKT.
Keiichiro Hashimoto will recount how he and his colleagues discovered MR1 (Hashimoto 2016): the discovery of its ligands was 20 years in the making! Since its discovery by Calabi and Milstein, the CD1 molecule has been known to be ancient, thought by some to predate or at least be as old as classical class I and class II MHC molecules; Kaufman and Rogers will discuss three different models of how this most ancient nonclassical class Ib molecule might have emerged in the vertebrates, and will also describe the evolution of the natural killer (NK) receptors NKPR-1 and their ligands (Kaufman and Rogers 2016). Reinick and Van Rhijn will then illustrate the expression and gene diversification of CD1 throughout the animal kingdom (Reinick and Van Rhijn 2016). Robert and colleagues have shown that innate-like T lymphocytes, and their recognition of class Ib molecules, are not simply features of warm-blooded vertebrates but also are prominent in frogs (Robert et al. 2016); these authors speculate that the innate T cell class Ib paradigm is present in all gnathostomes. MAIT cell activation, their MR1-presented
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