leprae), ,, ,, and have been shown to recognize specific mycobacterial antigens including the lipid mycolic acid, glycolipids such as lipoarabinomannan, glucose monomycolate, and mannosyl-β-1-phosphomycoketides, ,, , as well as lipopeptides such as the didehydroxymycobactins. T cells that are restricted by CD1a, CD1b, or CD1c have been implicated in human immune responses to mycobacterial infections ( M. As a result of these differences, different CD1 isoforms may carry out divergent antigen presenting functions. Additionally, CD1 isoforms are differentially expressed on antigen presenting cell (APC) types, with CD1d expressed broadly by myeloid APCs and B cells, and CD1a, CD1b, and CD1c showing more restricted patterns of expression. Antigen binding to CD1 molecules is thought to occur mainly in intracellular compartments, and since CD1a and CD1b clearly follow different intracellular trafficking routes than CD1c and CD1d, it is thought that different CD1 isoforms may access distinct types of antigens. In contrast to MHC-encoded antigen presenting molecules, CD1 molecules are specialized for binding lipid-containing antigens. Of these, CD1a-d have been shown to present antigens at the cell surface for recognition by T cells, while CD1e is expressed intracellularly and contributes to antigen loading and processing. There are five different CD1 isoforms, called CD1a, b, c, d and e, each of which is encoded by a distinct gene. None of the other authors have competing interests to declare.ĬD1 molecules are a family of β2-microglobulin-associated transmembrane glycoproteins that have a structure resembling class I molecules of the major histocompatibility complex (MHC). This affiliation does not alter adherence to the PLoS ONE policies on sharing data and materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: Gavin Painter and Regan Anderson are employees of Industrial Research Ltd., which is a limited liability company fully owned by the government of New Zealand. The role these authors played in this study was to prepare the synthetic glycolipid a-GalCer and to formulate it for injection into mice. GFP and RJA are employees of Industrial Research Ltd., which is a limited liability company fully owned by the government of New Zealand. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: Major funding for this work was from an award to JEG from the Pew Scholars Program in the Biomedical Sciences and from NIH grants R01AI060777 and R21AI076707 to JEG, and by a grant from the Medical Education and Research Committee of the Wisconsin Partnership Program to WJB. Received: ApAccepted: JPublished: June 30, 2011Ĭopyright: © 2011 Lockridge et al. PLoS ONE 6(6):Įditor: Jean Kanellopoulos, University Paris Sud, France (2011) Analysis of the CD1 Antigen Presenting System in Humanized SCID Mice. Thus, this system provides a new opportunity to study the role of CD1-related immune activation in infections to human-specific pathogens.Ĭitation: Lockridge JL, Chen X, Zhou Y, Rajesh D, Roenneburg DA, Hegde S, et al. Together, these results demonstrate that the human CD1 system is present and functionally competent in this humanized mouse model. CD1d tetramer staining directly identified human iNKT cells in spleen and liver samples from engrafted mice, and injection of the glycolipid antigen α-GalCer resulted in rapid elevation of human IFN-γ and IL-4 levels in the blood indicating that the human iNKT cells are biologically active in vivo. ELISpot analyses of splenocytes demonstrated the presence of CD1-reactive IFN-γ producing cells. APCs from spleen and liver were capable of presenting bacterial glycolipids to human CD1-restricted T cells. CD1 + cells were also detected in spleen, liver, and lungs. CD1a, b, c, and d isoforms were highly expressed by human thymocytes, and CD1a + cells with a dendritic morphology were present in the thymic medulla. Here we report that immune deficient mice engrafted with human fetal thymus, liver, and CD34 + hematopoietic stem cells develop a functional human CD1 compartment. CD1-dependent immune activation has been implicated in a wide range of immune responses, however, our understanding of the role of this pathway in human disease remains limited because of species differences between humans and other mammals: whereas humans express five different CD1 gene products (CD1a, CD1b, CD1c, CD1d, and CD1e), muroid rodents express only one CD1 isoform (CD1d). CD1 molecules are glycoproteins that present lipids and glycolipids for recognition by T cells.
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