Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule

被引:62
作者
VandenBussche, C. J. [1 ,2 ]
Mulrooney, T. J. [1 ,2 ]
Frazier, W. R. [1 ,2 ]
Dakshanamurthy, S. [1 ]
Hurley, C. K. [1 ]
机构
[1] Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Canc Ctr, Washington, DC 20057 USA
[2] Georgetown Univ, Med Ctr, Tumor Biol Training Program, Lombardi Canc Ctr, Washington, DC 20057 USA
关键词
natural killer cell; killer cell immunoglobulin-like receptors; cell surface receptor; NATURAL-KILLER-CELLS; INHIBITORY RECEPTOR; AMINO-ACID; HLA; RECOGNITION; GLYCOSYLATION; ACTIVATION; HLA-CW4; BINDING; PROTEIN;
D O I
10.1038/gene.2008.91
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Using flow cytometry, fluorescent microscopy and examination of receptor glycosylation status, we demonstrate that an entire killer cell immunoglobulin-like receptor (KIR) locus (KIR2DS3)-assumed earlier to be surface expressed-appears to have little appreciable surface expression in transfected cells. This phenotype was noted for receptors encoded by three allelic variants including the common KIR2DS3*001 allele. Comparing the surface expression of KIR2DS3 with that of the better-studied KIR2DS1 molecule in two different cell lines, mutational analysis identified multiple polymorphic amino-acid residues that significantly alter the proportion of molecules present on the cell surface. A simultaneous substitution of five residues localized to the leader peptide (residues -18 and -7), second domain (residues 123 and 150) and transmembrane region (residue 234) was required to restore KIR2DS3 to the expression level of KIR2DS1. Corresponding simultaneous substitutions of KIR2DS1 to the KIR2DS3 residues resulted in a dramatically decreased surface expression. Molecular modeling was used to predict how these substitutions contribute to this phenotype. Alterations in receptor surface expression are likely to affect the balance of immune cell signaling impacting the characteristics of the response to pathogens or malignancy.
引用
收藏
页码:162 / 173
页数:12
相关论文
共 32 条
[1]   A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele [J].
Anjos, S ;
Nguyen, A ;
Ounissi-Benkalha, H ;
Tessier, MC ;
Polychronakos, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (48) :46478-46486
[2]   Role of amino acid position 70 in the binding affinity of p50.1 and p58.1 receptors for HLA-Cw4 molecules [J].
Biassoni, R ;
Pessino, A ;
Malaspina, A ;
Cantoni, C ;
Bottino, C ;
Sivori, S ;
Moretta, L ;
Moretta, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (12) :3095-3099
[3]   Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population [J].
Bontadini, A. ;
Testi, M. ;
Cuccia, M. C. ;
Martinetti, M. ;
Carcassi, C. ;
Chiesa, A. ;
Cosentini, E. ;
Dametto, E. ;
Frison, S. ;
Iannone, A. M. ;
Lombardo, C. ;
Malagoli, A. ;
Mariani, M. ;
Mariotti, L. ;
Mascaretti, L. ;
Mele, L. ;
Miotti, V. ;
Nesci, S. ;
Ozzella, G. ;
Piancatelli, D. ;
Romeo, G. ;
Tagliaferri, C. ;
Vatta, S. ;
Andreani, M. ;
Conte, R. .
JOURNAL OF TRANSLATIONAL MEDICINE, 2006, 4 (1)
[4]  
Campbell KS, 1998, EUR J IMMUNOL, V28, P599, DOI 10.1002/(SICI)1521-4141(199802)28:02<599::AID-IMMU599>3.0.CO
[5]  
2-F
[6]   Cutting edge:: KIR3DS1, a gene implicated in resistance to progression to AIDS, encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell activation [J].
Carr, William H. ;
Rosen, David B. ;
Arase, Hisashi ;
Nixon, Douglas F. ;
Michaelsson, Jakob ;
Lanier, Lewis L. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (02) :647-651
[7]   Evidence that the KIR2DS5 gene codes for a surface receptor triggering natural killer cell function [J].
Della Chiesa, Mariella ;
Romeo, Elisa ;
Falco, Michela ;
Balsamo, Mirna ;
Augugliaro, Raffaella ;
Moretta, Lorenzo ;
Bottino, Cristina ;
Moretta, Alessandro ;
Vitale, Massimo .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (08) :2284-2289
[8]   Alternatively spliced forms of human killer inhibitory receptors [J].
Dohring, C ;
Samaridis, J ;
Colonna, M .
IMMUNOGENETICS, 1996, 44 (03) :227-230
[9]   Glycosylation of FcγRIII in N163 as mechanism of regulating receptor affinity [J].
Drescher, B ;
Witte, T ;
Schmidt, RE .
IMMUNOLOGY, 2003, 110 (03) :335-340
[10]   Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors [J].
Fan, QR ;
Mosyak, L ;
Winter, CC ;
Wagtmann, N ;
Long, EO ;
Wiley, DC .
NATURE, 1997, 389 (6646) :96-100