Volume 15 Issue 3, March 2005: 176-182
ORIGINAL ARTICLES
Residues met76 and gln79 in HLA-G α1 domain involved in KIR2DL4 recognition
Wei Hua YAN1,2,*, Li An FAN1,2,**
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
Correspondence: Li An FAN(Lian_Fan@online.sh.cn)
>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 α1 domain
is an important killer cell Ig-like receptor (KIR) recognition site and
the Met
76 and Gln
79 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 Met
76, Gln
79
mutated
to
Ala
76,79 in the α1
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 Met
76 and Gln
79 in HLA-G α1 domain
plays a critical role in the recognition of KIR2DL4, which could be an
explanation for the isoforms of HLA-G, all containing the α1 domain,
with the potential to regulate NK functions.
FULL TEXT | PDF
Browse 2029
