A novel role of CD1c in regulating CD1d-mediated NKT cell recognition by competitive binding to Ig-like transcript 4.
Humans express four MHC-like CD1 molecules CD1a, b, c and d that are capable of presenting a wide variety of self or foreign lipid antigens to T cells. Much progress has been made in elucidating the function of CD1d-restricted NKT cells in both innate and adaptive immune responses. However, knowledge of the other CD1 molecules is less well defined in terms of lipid presentation and immune regulation. We have previously shown that immunoglobulin-like transcript 4 (ILT4) binds to CD1d and inhibits its recognition by NKT cells. In this study, we show that CD1c can also interact specifically with ILT4 with a higher affinity than that of CD1d. Furthermore, changes in CD1c expression seem to modulate CD1d function; up-regulation of CD1c enhances NKT recognition of CD1d and down-regulation reduces CD1d recognition. We propose that CD1c can act as a sink for the inhibitory receptor ILT4: when CD1c is up-regulated, ILT4 is recruited to CD1c, thus reducing the inhibitory effect of ILT4 on CD1d recognition. Consequently, CD1c could be a potential target for modulating NKT activity.


BACKGROUND
NKT, CD1d, CD1c, ILT4, antigen presentation.
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford, UK. demin.li@ndcls.ox.ac.uk
Demin
D
Li
An
A
Hong
Qiong
Q
Lu
George F
GF
Gao
Boquan
B
Jin
Gavin R
GR
Screaton
Xiao-Ning
XN
Xu
D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D034622:RNA Interference; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020349:Surface Plasmon Resonance; D015854:Up-Regulation / Q000276:immunology
D018949:Antigens, CD1; D055610:Antigens, CD1d; C437944:CD1C protein, human; C526877:CD1D protein, human; D006023:Glycoproteins; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic