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Brigl, Manfred

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Brigl

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Manfred

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Brigl, Manfred
Author's Publications: search.filters.isAuthorOfPublication.46334d7f-8c4a-44d4-8b57-bb416475adeb

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    Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells
    (2013) Cohen, Nadia R.; Brennan, Patrick; Shay, Tal; Watts, Gerald; Brigl, Manfred; Kang, Joonsoo; Brenner, Michael
    Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled iNKT cell gene expression during ontogeny and in peripheral subsets as part of the Immunological Genome Project (ImmGen). High-resolution comparative transcriptional analyses defined developmental and subset-specific iNKT cell gene expression programs. In addition, iNKT cells were found to share an extensive transcriptional program with natural killer (NK) cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Strikingly, the NK- iNKT program also operated constitutively in γδT cells and in adaptive T cells following activation. Together, our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes.
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    The Extended Family of CD1d-Restricted NKT Cells: Sifting through a Mixed Bag of TCRs, Antigens, and Functions
    (Frontiers Media S.A., 2015) Macho-Fernandez, Elodie; Brigl, Manfred
    Natural killer T (NKT) cells comprise a family of specialized T cells that recognize lipid antigens presented by CD1d. Based on their T cell receptor (TCR) usage and antigen specificities, CD1d-restricted NKT cells have been divided into two main subsets: type I NKT cells that use a canonical invariant TCR α-chain and recognize α-galactosylceramide (α-GalCer), and type II NKT cells that use a more diverse αβ TCR repertoire and do not recognize α-GalCer. In addition, α-GalCer-reactive NKT cells that use non-canonical αβ TCRs and CD1d-restricted T cells that use γδ or δ/αβ TCRs have recently been identified, revealing further diversity among CD1d-restricted T cells. Importantly, in addition to their distinct antigen specificities, functional differences are beginning to emerge between the different members of the CD1d-restricted T cell family. In this review, while using type I NKT cells as comparison, we will focus on type II NKT cells and the other non-invariant CD1d-restricted T cell subsets, and discuss our current understanding of the antigens they recognize, the formation of stimulatory CD1d/antigen complexes, the modes of TCR-mediated antigen recognition, and the mechanisms and consequences of their activation that underlie their function in antimicrobial responses, anti-tumor immunity, and autoimmunity.
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    Synthesis and Biological Activity of α-Galactosyl Ceramide KRN7000 and Galactosyl (α1→2) Galactosyl Ceramide
    (Elsevier Science Ltd, 2009) Veerapen, Natacha; Brigl, Manfred; Garg, Salil; Cerundolo, Vincenzo; Cox, Liam R.; Brenner, Michael; Besra, Gurdyal S.
    We herein report a faster and less cumbersome synthesis of the biologically attractive, α-galactosyl ceramide (α-GalCer), known as KRN7000, and its analogues. More importantly, the use of a silicon tethered intramolecular glycosylation reaction gave easy access to the diglycosyl ceramide Gal(α1→2)GalCer, which has been shown to require uptake and processing to the biologically active α-GalCer derivative.