CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution.

Abstract

Natural killer (NK) T cells are a lymphocyte subset with a distinct surface phenotype, an invariant T cell receptor (TCR), and reactivity to CD1. Here we show that mouse NK T cells can recognize human CD1d as well as mouse CD1, and human NK T cells also recognize both CD1 homologues. The unprecedented degree of conservation of this T cell recognition system suggests that it is fundamentally important. Mouse or human CD1 molecules can present the glycolipid alpha-galactosylceramide (alpha-GalCer) to NK T cells from either species. Human T cells, preselected for invariant Valpha24 TCR expression, uniformly recognize alpha-GalCer presented by either human CD1d or mouse CD1. In addition, culture of human peripheral blood cells with alpha-GalCer led to the dramatic expansion of NK T cells with an invariant (Valpha24(+)) TCR and the release of large amounts of cytokines. Because invariant Valpha14(+) and Valpha24(+) NK T cells have been implicated both in the control of autoimmune disease and the response to tumors, our data suggest that alpha-GalCer could be a useful agent for modulating human immune responses by activation of the highly conserved NK T cell subset.

• Authors: L Brossay, M Chioda, N Burdin, Y Koezuka, G Casorati, P Dellabona, M Kronenberg
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 188 Issue 8 Pg. 1521-8 (Oct 19 1998) ISSN: 0022-1007 [Print] United States
• PMID: 9782129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD1
• Ceramides
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Animals
• Antigen Presentation
• Antigens, CD1 (physiology)
• Biological Evolution
• Cell Line
• Ceramides (metabolism, pharmacology)
• Humans
• Hybridomas
• Killer Cells, Natural (drug effects, immunology)
• Mice
• Receptors, Antigen, T-Cell, alpha-beta (analysis)