ARTICLE

Cell Research, 15(3):176-182, Mar 2005

Residues met⁷⁶ and gln⁷⁹ in HLA-G ¦Á1 domain involved in KIR2DL4 recognition

Wei Hua YAN^1,2,*, Li An FAN^1,2,**

¹Laboratory of Immunogenetics, Shanghai Second Medical University, 280 South Chongqing Road, Shanghai 200025, China
²Laboratory of Immunogenetics, Shanghai Institute of Immunology, 280 South Chongqing Road, Shanghai 200025, China

Received, Nov 9, 2004   Revised, Jan 2, 2005   Accepted, Feb 3, 2005

*Current address: Laboratory Center, Wenzhou Medical College Affiliated Taizhou Hospital, LinHai, Zhejiang 317000, China

Correspondence: Li An FAN +86-21-63846590-776541(ext.) (phone) +86-21-63846383 (fax) Lian_Fan@online.sh.cn

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Abstract

Human leukocyte antigen-G (HLA-G) has long been speculated as a beneficial factor for a successful pregnancy for its restricted expression on fetal-maternal extravillous cytotrophoblasts and its capability of modulating uterine natural killer cell (uNK) function such as cytotoxicity and cytokine production through NK cell receptors. HLA class I ¦Á1 domain is an important killer cell Ig-like receptor (KIR) recognition site and the Met⁷⁶ and Gln⁷⁹ are unique to HLA-G in this region. NK cell receptor KIR2DL4 is a specific receptor for HLA-G, yet the recognition site on HLA-G remains unknown. In this study, retroviral transduction was applied to express the wild type HLA-G (HLA-wtG), mutant HLA-G (HLA-mG) on the chronic myelogenous leukemia cell line K562 cells and KIR2DL4 molecule on NK-92 cells, respectively. KIR2DL4-IgG Fc fusion protein was generated to determine the binding specificity between KIR2DL4 and HLA-G. Our results showed that residue Met⁷⁶, Gln⁷⁹ mutated to Ala^76,79 in the ¦Á1 domain of HLA-G protein could affect the binding affinity between KIR2DL4 and HLA-G, meanwhile, the KIR2DL4 transfected NK-92 cells (NK-92-2DL4) showed a considerably different cytolysis ability against the HLA-wtG and HLA-mG transfected K562 targets. Taken together, our data indicated that residue Met⁷⁶ and Gln⁷⁹ in HLA-G ¦Á1 domain plays a critical role in the recognition of KIR2DL4, which could be an explanation for the isoforms of HLA-G, all containing the ¦Á1 domain, with the potential to regulate NK functions.

Keywords: NK cell, KIR2DL4, HLA-G, receptor.