cd1 antigens


Summary: Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.

Top Publications

  1. Paget C, Mallevaey T, Speak A, Torres D, Fontaine J, Sheehan K, et al. Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids. Immunity. 2007;27:597-609 pubmed
    ..These data underline the role of TLR9 in iNKT cell activation and might have relevance to infectious diseases and cancer. ..
  2. Cohen N, Garg S, Brenner M. Antigen Presentation by CD1 Lipids, T Cells, and NKT Cells in Microbial Immunity. Adv Immunol. 2009;102:1-94 pubmed publisher
    ..In this review, we describe the pathways and mechanisms of lipid antigen binding and presentation by CD1 in detail, as well as the diverse roles played by CD1-restricted T cells in the context of microbial infection. ..
  3. Chen X, Wang X, Keaton J, Reddington F, Illarionov P, Besra G, et al. Distinct endosomal trafficking requirements for presentation of autoantigens and exogenous lipids by human CD1d molecules. J Immunol. 2007;178:6181-90 pubmed
    ..These results indicate that autoantigens and exogenous lipids are acquired by human CD1d at distinct cellular locations, and that Ii trafficking selectively regulates CD1d-mediated presentation of extracellular Ags. ..
  4. Piccioli D, Tavarini S, Borgogni E, Steri V, Nuti S, Sammicheli C, et al. Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets. Blood. 2007;109:5371-9 pubmed
    ..In conclusion, CD16-mDCs show strong proinflammatory activity, whereas CD1c-mDCs appear to be mainly inducers of chemotaxis. ..
  5. Prete S, Giuliani A, D Atri S, Graziani G, Balduzzi A, Oggioni M, et al. BCG-infected adherent mononuclear cells release cytokines that regulate group 1 CD1 molecule expression. Int Immunopharmacol. 2007;7:321-32 pubmed
    ..It cannot be excluded that this mechanism could play a role in the limited efficiency of BCG vaccination. ..
  6. Zajonc D, Ainge G, Painter G, Severn W, Wilson I. Structural characterization of mycobacterial phosphatidylinositol mannoside binding to mouse CD1d. J Immunol. 2006;177:4577-83 pubmed
  7. Hager E, Hawwari A, Matsuda J, Krangel M, Gapin L. Multiple constraints at the level of TCRalpha rearrangement impact Valpha14i NKT cell development. J Immunol. 2007;179:2228-34 pubmed
    ..Altogether, this study provides evidence that there is no directed rearrangement of Valpha14 to Jalpha18 segments and supports the instructive selection model for NKT cell selection. ..
  8. Borg N, Wun K, Kjer Nielsen L, Wilce M, Pellicci D, Koh R, et al. CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature. 2007;448:44-9 pubmed
    ..These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system. ..
  9. McCarthy C, Shepherd D, Fleire S, Stronge V, Koch M, Illarionov P, et al. The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation. J Exp Med. 2007;204:1131-44 pubmed
    ..This indirect effect provides a general mechanism by which lipid-specific lymphocytes are capable of recognizing both the group head and the length of lipid antigens, ensuring greater specificity of antigen recognition. ..

More Information


  1. Gadola S, Silk J, Jeans A, Illarionov P, Salio M, Besra G, et al. Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J Exp Med. 2006;203:2293-303 pubmed
    ..These data suggest that GSL storage may result in alterations in thymic selection of iNKT cells caused by impaired presentation of selecting ligands. ..
  2. de Jong A, Arce E, Cheng T, van Summeren R, Feringa B, Dudkin V, et al. CD1c presentation of synthetic glycolipid antigens with foreign alkyl branching motifs. Chem Biol. 2007;14:1232-42 pubmed
    ..Therefore, the preferential recognition of branched lipids may represent a new lipid-based pathogen-associated molecular pattern. ..
  3. Barral D, Brenner M. CD1 antigen presentation: how it works. Nat Rev Immunol. 2007;7:929-41 pubmed
  4. Zajonc D, Savage P, Bendelac A, Wilson I, Teyton L. Crystal structures of mouse CD1d-iGb3 complex and its cognate Valpha14 T cell receptor suggest a model for dual recognition of foreign and self glycolipids. J Mol Biol. 2008;377:1104-16 pubmed publisher
    ..Thus, the same TCR may adopt alternative modes of recognition for these foreign and self-ligands for NKT cell activation. ..
  5. Ochoa M, Loncaric A, Krutzik S, Becker T, Modlin R. "Dermal dendritic cells" comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages. J Invest Dermatol. 2008;128:2225-31 pubmed publisher
    ..These data suggest that dermal dendritic-appearing macrophages comprise a novel part of the innate immune response in the resident skin immune system. ..
  6. Godfrey D, Rossjohn J, McCluskey J. The fidelity, occasional promiscuity, and versatility of T cell receptor recognition. Immunity. 2008;28:304-14 pubmed publisher
    ..Collectively, these studies have revealed the versatility of the TCR in recognizing the distinct yet evolutionarily related proteinaceous and lipid-presenting molecules of the immune system. ..
  7. Relloso M, Cheng T, Im J, Parisini E, Roura Mir C, DeBono C, et al. pH-dependent interdomain tethers of CD1b regulate its antigen capture. Immunity. 2008;28:774-86 pubmed publisher
    ..We propose that ionic tethers act as molecular switches that respond to pH fluxes during endosomal recycling and regulate the conformation of the CD1 heavy chain to control the size and rate of antigens captured. ..
  8. Raftery M, Winau F, Giese T, Kaufmann S, Schaible U, Schönrich G. Viral danger signals control CD1d de novo synthesis and NKT cell activation. Eur J Immunol. 2008;38:668-79 pubmed publisher
    ..In conclusion, our data indicate that viral danger signals trigger NKT cell activation by enhancing CD1d de novo synthesis through increasing the abundance of CD1D mRNA in human myeloid DC. ..
  9. Gustafson J, Eklund C, Wallström M, Zellin G, Magnusson B, Hassèus B. Langerin-expressing and CD83-expressing cells in oral lichen planus lesions. Acta Odontol Scand. 2007;65:156-61 pubmed
    ..The presence of CD83+ dendritic cells in areas of lymphocyte clusters in the connective tissue of OLP lesions indicates the possibility of ongoing autoantigen presentation. ..
  10. Layre E, Collmann A, Bastian M, Mariotti S, Czaplicki J, Prandi J, et al. Mycolic acids constitute a scaffold for mycobacterial lipid antigens stimulating CD1-restricted T cells. Chem Biol. 2009;16:82-92 pubmed publisher
  11. Gagliardi M, Lemassu A, Teloni R, Mariotti S, Sargentini V, Pardini M, et al. Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis to block CD1 molecule expression and disable the function of dendritic cell derived from infected monocyte. Cell Microbiol. 2007;9:2081-92 pubmed
    ..Thus, we propose a mechanism of Mtb-monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses. ..
  12. Yuan W, Qi X, Tsang P, Kang S, Illarionov P, Illaniorov P, et al. Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules. Proc Natl Acad Sci U S A. 2007;104:5551-6 pubmed
    ..The optimal pH for saposin B-mediated lipid binding to CD1d, pH 6, is higher than that of lysosomes, suggesting that saposin B may facilitate lipid binding to CD1d molecules throughout the endocytic pathway. ..
  13. Musso T, Scutera S, Vermi W, Daniele R, Fornaro M, Castagnoli C, et al. Activin A induces Langerhans cell differentiation in vitro and in human skin explants. PLoS ONE. 2008;3:e3271 pubmed publisher
  14. Dougan S, Kaser A, Blumberg R. CD1 expression on antigen-presenting cells. Curr Top Microbiol Immunol. 2007;314:113-41 pubmed
    ..Altered expression of CD 1 in cancer, autoimmunity, and infectious disease is well documented, and the implication of CD 1 expression in these diseases is discussed. ..
  15. Lappas C, Day Y, Marshall M, Engelhard V, Linden J. Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation. J Exp Med. 2006;203:2639-48 pubmed
    ..These findings suggest that hepatic reperfusion injury is initiated by the CD1d-dependent activation of NKT cells, and the activation of these cells is inhibited by A2AR activation. ..
  16. Colmone A, Li S, Wang C. Activating transcription factor/cAMP response element binding protein family member regulated transcription of CD1A. J Immunol. 2006;177:7024-32 pubmed
    ..The fact that these factors also bind the CD1A promoter in human monocytes strongly suggests a role for ATF/CREB family members in regulation of CD1A expression. ..
  17. Kinjo Y, Tupin E, Wu D, Fujio M, Garcia Navarro R, Benhnia M, et al. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol. 2006;7:978-86 pubmed
  18. Moody D. TLR gateways to CD1 function. Nat Immunol. 2006;7:811-7 pubmed
  19. Salio M, Speak A, Shepherd D, Polzella P, Illarionov P, Veerapen N, et al. Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation. Proc Natl Acad Sci U S A. 2007;104:20490-5 pubmed
    ..The ability of innate stimuli to modulate the lipid profile of APCs resulting in iNKT cell activation and APC maturation underscores the role of iNKT cells in assisting priming of antigen-specific immune responses. ..
  20. Freeman C, Curtis J, Chensue S. CC chemokine receptor 5 and CXC chemokine receptor 6 expression by lung CD8+ cells correlates with chronic obstructive pulmonary disease severity. Am J Pathol. 2007;171:767-76 pubmed
    ..Chemokine targeting may prove to be a viable treatment approach. ..
  21. Kaser A, Hava D, Dougan S, Chen Z, Zeissig S, Brenner M, et al. Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules. Eur J Immunol. 2008;38:2351-9 pubmed publisher
    ..Thus, these studies indicate that MTP, despite its ER localization, regulates endogenous as well as exogenous lipid antigen presentation, and suggest a broad role for MTP in the regulation of CD1 antigen presentation. ..
  22. Dascher C. Evolutionary biology of CD1. Curr Top Microbiol Immunol. 2007;314:3-26 pubmed
    ..In contrast, CD1 genes have thus far been found only in a subset of these animal groups. This pattern of CD1 occurrence in the genomes of living species suggests the emergence of CD 1 in an early terrestrial vertebrate. ..
  23. Sakuishi K, Oki S, Araki M, Porcelli S, Miyake S, Yamamura T. Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. J Immunol. 2007;179:3452-62 pubmed
    ..The iNKT cell subset producing IL-5 and IL-13 could play a major role in the development of allergic disease or asthma and also in the immune regulation of Th1 inflammation. ..
  24. Schuster C, Vaculik C, Fiala C, Meindl S, Brandt O, Imhof M, et al. HLA-DR+ leukocytes acquire CD1 antigens in embryonic and fetal human skin and contain functional antigen-presenting cells. J Exp Med. 2009;206:169-81 pubmed publisher
    ..Collectively, our data provide insight into skin DC biology and the mechanisms through which skin DCs presumably populate the skin during development. ..
  25. Scott Browne J, Matsuda J, Mallevaey T, White J, Borg N, McCluskey J, et al. Germline-encoded recognition of diverse glycolipids by natural killer T cells. Nat Immunol. 2007;8:1105-13 pubmed
  26. Kasmar A, Van Rhijn I, Moody D. The evolved functions of CD1 during infection. Curr Opin Immunol. 2009;21:397-403 pubmed publisher
    ..Viewed from the perspective that CD1 is a diverse gene family that activates several of classes of T cells, new insights into lipid loading and infection response are emerging. ..
  27. Bendelac A, Savage P, Teyton L. The biology of NKT cells. Annu Rev Immunol. 2007;25:297-336 pubmed
  28. Yang J, Wen X, Liu H, Folayan G, Dong X, Zhou M, et al. Examining the role of CD1d and natural killer T cells in the development of nephritis in a genetically susceptible lupus model. Arthritis Rheum. 2007;56:1219-33 pubmed
    ..This finding, together with reduced thymic iNKT cells in young BWF1 mice as compared with nonautoimmune strains, implies a regulatory role of CD1d and iNKT cells during the development of lupus. ..
  29. Sugita M, Barral D, Brenner M. Pathways of CD1 and lipid antigen delivery, trafficking, processing, loading, and presentation. Curr Top Microbiol Immunol. 2007;314:143-64 pubmed
    ..Defects in these pathways result in impaired T cell development and function, underscoring their critical role in the lipid-specific T cell immune responses. ..
  30. Urban B, Cordery D, Shafi M, Bull P, Newbold C, Williams T, et al. The frequency of BDCA3-positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria. Infect Immun. 2006;74:6700-6 pubmed
  31. Ko C, Kim J, Phan J, Binder S. Bcl-2-positive epidermal dendritic cells in inverted follicular keratoses but not squamous cell carcinomas or seborrheic keratoses. J Cutan Pathol. 2006;33:498-501 pubmed
    ..01). SCCs showed bcl-2-positive cells only within the basal layer of the normal epidermis flanking the carcinomas. These results suggest that there is different bcl-2 regulation of CD1a-positive cells in IFKs, SKs, and SCCs. ..
  32. Yuan W, Dasgupta A, Cresswell P. Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling. Nat Immunol. 2006;7:835-42 pubmed
    ..Such inhibition of CD1d surface expression impaired antigen-presenting cell-mediated stimulation of natural killer T cells, supporting the idea that this mechanism may be an important HSV-1 immune evasion strategy. ..
  33. Stronge V, Salio M, Jones E, Cerundolo V. A closer look at CD1d molecules: new horizons in studying NKT cells. Trends Immunol. 2007;28:455-62 pubmed
    ..Here we review new reagents and novel protocols that are facilitating a closer look at lipid presentation by CD1d molecules and their recognition by iNKT cells. ..
  34. Brutkiewicz R. CD1d ligands: the good, the bad, and the ugly. J Immunol. 2006;177:769-75 pubmed
    ..They can also be protective in autoimmune diseases or cancer or can be deleterious. This review will highlight these ligands in a discussion of their potential use against (and role in the pathogenesis of) these diseases. ..
  35. Tsoumakidou M, Kemp S, Thorley A, Zhu J, Dewar A, Jeffery P, et al. Expression of blood dendritic cell antigens (BDCAs) by CD1a+ human pulmonary cells. Respir Med. 2009;103:935-8 pubmed publisher
  36. Hava D, van der Wel N, Cohen N, Dascher C, Houben D, Leon L, et al. Evasion of peptide, but not lipid antigen presentation, through pathogen-induced dendritic cell maturation. Proc Natl Acad Sci U S A. 2008;105:11281-6 pubmed publisher
  37. Barral D, Cavallari M, McCormick P, Garg S, Magee A, Bonifacino J, et al. CD1a and MHC class I follow a similar endocytic recycling pathway. Traffic. 2008;9:1446-57 pubmed publisher
    ..Furthermore, we identify CD1a as a new marker for the clathrin- and dynamin-independent and DRM-dependent pathway of internalization as well as the Rab22a- and ARF6-dependent recycling pathway. ..
  38. Looringh van Beeck F, Zajonc D, Moore P, Schlotter Y, Broere F, Rutten V, et al. Two canine CD1a proteins are differentially expressed in skin. Immunogenetics. 2008;60:315-24 pubmed publisher
    ..cDNA sequencing and expressed sequence tag sequences confirmed the existence of a short, human CD1a-like cytoplasmic tail of four amino acids, of an intermediate length form of 15 amino acids, and of a long form of 31 amino acids. ..
  39. Sriram V, Du W, Gervay Hague J, Brutkiewicz R. Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells. Eur J Immunol. 2005;35:1692-701 pubmed
    ..Further studies on the S. paucimobilis GSL could potentially lead to other natural sources of CD1d-specific ligands useful for NKT cell analyses and aimed at identifying novel therapies for a variety of disease states. ..
  40. De Libero G, Mori L. Recognition of lipid antigens by T cells. Nat Rev Immunol. 2005;5:485-96 pubmed
    ..A greater understanding of lipid-specific T cells and the molecular mechanisms of lipid immunogenicity should facilitate the development of lipid-based vaccines. ..
  41. Koch M, Stronge V, Shepherd D, Gadola S, Mathew B, Ritter G, et al. The crystal structure of human CD1d with and without alpha-galactosylceramide. Nat Immunol. 2005;6:819-26 pubmed
    ..These structures provide clues as to how CD1 molecules load glycolipids as well as data to guide the design of new therapeutic agents. ..
  42. Godfrey D, McCluskey J, Rossjohn J. CD1d antigen presentation: treats for NKT cells. Nat Immunol. 2005;6:754-6 pubmed
  43. van den Elzen P, Garg S, Leon L, Brigl M, Leadbetter E, Gumperz J, et al. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature. 2005;437:906-10 pubmed
    ..Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens. ..
  44. Brigl M, van den Elzen P, Chen X, Meyers J, Wu D, Wong C, et al. Conserved and heterogeneous lipid antigen specificities of CD1d-restricted NKT cell receptors. J Immunol. 2006;176:3625-34 pubmed
  45. Gadola S, Koch M, Marles Wright J, Lissin N, Shepherd D, Matulis G, et al. Structure and binding kinetics of three different human CD1d-alpha-galactosylceramide-specific T cell receptors. J Exp Med. 2006;203:699-710 pubmed
    ..This docking provides an explanation for the dominant usage of Vbeta11 and Vbeta8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d-alpha-GalCer. ..
  46. Wu D, Zajonc D, Fujio M, Sullivan B, Kinjo Y, Kronenberg M, et al. Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d. Proc Natl Acad Sci U S A. 2006;103:3972-7 pubmed
  47. Van Rhijn I, Koets A, Im J, Piebes D, Reddington F, Besra G, et al. The bovine CD1 family contains group 1 CD1 proteins, but no functional CD1d. J Immunol. 2006;176:4888-93 pubmed
    ..Cattle can be used as a model to study group 1 CD1-restricted T cell immunity, including its role in the defense against mycobacterial infections that occur naturally in this species. ..
  48. Manolova V, Kistowska M, Paoletti S, Baltariu G, Bausinger H, Hanau D, et al. Functional CD1a is stabilized by exogenous lipids. Eur J Immunol. 2006;36:1083-92 pubmed
    ..These results indicate a functional dichotomy between CD1a and CD1b molecules and provide new information on how the lipid antigenic repertoire is immunologically sampled. ..
  49. Wei D, Curran S, Savage P, Teyton L, Bendelac A. Mechanisms imposing the Vbeta bias of Valpha14 natural killer T cells and consequences for microbial glycolipid recognition. J Exp Med. 2006;203:1197-207 pubmed
  50. Sagiv Y, Hudspeth K, Mattner J, Schrantz N, Stern R, Zhou D, et al. Cutting edge: impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein. J Immunol. 2006;177:26-30 pubmed
    ..These findings reveal a blockade of lipid trafficking between endosome and lysosome as a consequence of NPC1 deficiency and suggest a common mechanism for the defects in lipid presentation and development of Valpha14-Jalpha18 NKT cells. ..
  51. Cheng T, Relloso M, Van Rhijn I, Young D, Besra G, Briken V, et al. Role of lipid trimming and CD1 groove size in cellular antigen presentation. EMBO J. 2006;25:2989-99 pubmed
    ..Lipids are loaded in an intact form, so that they likely protrude through a portal near the bottom of the groove, which represents an escape hatch for long lipids from mycobacterial pathogens. ..
  52. Schumann J, Mycko M, Dellabona P, Casorati G, MacDonald H. Cutting edge: influence of the TCR Vbeta domain on the selection of semi-invariant NKT cells by endogenous ligands. J Immunol. 2006;176:2064-8 pubmed
    ..Collectively, our data demonstrate that the TCR Vbeta domain influences the selection of Valpha14i NKT cells by endogenous ligands, presumably because Vbeta7 confers higher avidity binding. ..
  53. Vincent M, Xiong X, Grant E, Peng W, Brenner M. CD1a-, b-, and c-restricted TCRs recognize both self and foreign antigens. J Immunol. 2005;175:6344-51 pubmed
    ..The dual reactivity of these CD1-restricted cells suggests that the capacity for rapid responses to inflammatory stimuli without memory coexists with the capacity for strong Ag-specific responses and the generation of memory in vivo. ..