Donor Unrestricted T Cells: A Shared Human T Cell Response

Rhijn, Ildiko Van; Moody, D. Branch

doi:10.4049/jimmunol.1500943

Cited by 70 publications

(92 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TCRαβ + CD1b-restricted mycolate-specific GEM lymphocytes are a conserved T cell population in humans which expand upon Mtb infection and exhibit potent anti-mycobacterial effector functions through production of IFN-γ and TNF-α (9,31,37,38). Our demonstration of CD1b expression within human lung TB granulomas provides further evidence for lipid-specific T cell immunity in host defence against TB.…”

Section: Discussionmentioning

confidence: 59%

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Chancellor

Tocheva

Cave-Ayland

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Tuberculosis, caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in tuberculosis granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells. Mycobaterium tuberculosis | GEM T cells | CD1b | Mycolate lipids |

show abstract

Section: Discussionmentioning

confidence: 59%

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Chancellor

Tocheva

Cave-Ayland

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Thus, the concept of MHC-restricted TCRs is invoked in the particular situation of shared antigen exposure and matched MHC genes, which is not the usual setting of T cell activation in disease. In contrast, the V and J rearrangements that define NKT and MAIT TCRα chains are conserved broadly across most humans or mice, based on their recognition of a universally expressed antigen-presenting molecule (Porcelli et al 1993; Tilloy et al 1999; Huang et al 2005; Van Rhijn et al 2015a; Van Rhijn and Moody 2015; Boudinot et al 2016). These invariant TCRs are much more public than any MHC-restricted TCR and can be thought of as universal in a species.…”

Section: Beyond Public Tcrsmentioning

confidence: 99%

Donor-unrestricted T cells in the human CD1 system

Huang

Moody

2016

Immunogenetics

Self Cite

View full text Add to dashboard Cite

The CD1 and MHC systems are specialized for lipid and peptide display, respectively. Here, we review evidence showing how cellular CD1a, CD1b, CD1c, and CD1d proteins capture and display many cellular lipids to T cell receptors (TCRs). Increasing evidence shows that CD1-reactive T cells operate outside two classical immunogenetic concepts derived from the MHC paradigm. First, because CD1 proteins are non-polymorphic in human populations, T cell responses are not restricted to the donor’s genetic background. Second, the simplified population genetics of CD1 antigen-presenting molecules can lead to simplified patterns of TCR usage. As contrasted with donor-restricted patterns of MHC-TCR interaction, the donor-unrestricted nature of CD1-TCR interactions raises the prospect that lipid agonists and antagonists of T cells could be developed.

show abstract

“…Invariant natural killer T (iNKT) cells express an invariant CD1d-restricted TCR and have innate-like characteristics (1, 2). iNKT cells respond rapidly in an innate manner with a broad range of effector and immune-regulatory functions upon recognition of glycolipid antigens presented by CD1d (3, 4).…”

Section: Introductionmentioning

confidence: 99%

Innate Invariant NKT Cell Recognition of HIV-1–Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion

Paquin‐Proulx

Gibbs

Bächle

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Invariant natural killer T (iNKT) cells are innate-like T cells that respond rapidly with a broad range of effector functions upon recognition of glycolipid antigens presented by CD1d. HIV-1 carries Nef- and Vpu-dependent mechanisms to interfere with CD1d surface expression, indirectly suggesting a role for iNKT cells in control of HIV-1 infection. Here, we investigated if iNKT cells can participate in the innate cell-mediated immune response to HIV-1. Infection of dendritic cells (DCs) with Nef- and Vpu-deficient HIV-1 induced upregulation of CD1d in a TLR7-dependent manner. Infection of DCs caused modulation of enzymes in the sphingolipid pathway and enhanced expression of the endogenous glucocylceramide antigen. Importantly, iNKT cells responded specifically to rare DCs productively infected with Nef- and Vpu-defective HIV-1. Transmitted founder viral isolates differed in their CD1d down-regulation capacity, suggesting that diverse strains may be differentially successful in inhibiting this pathway. Furthermore, both iNKT cells and DCs expressing CD1d and HIV-receptors resided in the female genital mucosa, a site where HIV-1 transmission occurs. Together, these findings suggest that innate iNKT cell sensing of HIV-1 infection in DCs is an early immune detection mechanism, which is independent of priming and adaptive recognition of viral antigen, and is actively targeted by Nef- and Vpu-dependent viral immune evasion mechanisms.

show abstract

Donor Unrestricted T Cells: A Shared Human T Cell Response

Cited by 70 publications

References 69 publications

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Donor-unrestricted T cells in the human CD1 system

Innate Invariant NKT Cell Recognition of HIV-1–Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion

Contact Info

Product

Resources

About