Impaired spontaneous endocytosis of HLA-G.
HLA-G is a class Ib (non-classical) major histocompatibility complex (MHC) protein expressed at the maternal-fetal interface that inhibits natural killer (NK) cell-mediated lysis in an allotype-independent manner. Here we report that the spontaneous endocytosis of HLA-G is severely reduced because of its short cytoplasmic tail. Class I (classical) MHC proteins on the surface of B cell transfectants detected by primary and secondary antibodies underwent endocytosis at a moderate rate, whereas HLA-G, chimeric proteins consisting of the extracellular domains of HLA-C with the C-terminal sequence of HLA-G, or glycophosphatidylinositol-tailed HLA-C proteins, were not efficiently internalized. In addition, a mutant of beta 2-microglobulin (Ser88Cys) that could be specifically labeled with Texas red (or other fluorescent probes) and exchanged into class I or class Ib MHC proteins was employed to study spontaneous internalization of MHC proteins by a non-perturbative method independent of an antibody ligand. These data are discussed in terms of both the role of HLA-G expressed on the fetal trophoblast and the function of the cytoplasmic tail in class I MHC proteins.
Davis
D M
DM
Department of Molecular and Cellular Biology, Harvard University, Cambridge 02138, USA.
Reyburn
H T
HT
Pazmany
L
L
Chiu
I
I
Mandelboim
O
O
Strominger
J L
JL
D001402:B-Lymphocytes / Q000378:metabolism*; D004705:Endocytosis; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015236:HLA-C Antigens / Q000235:genetics / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology; D014966:Xanthenes; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
D005456:Fluorescent Dyes; D006680:HLA Antigens; D015236:HLA-C Antigens; C040178:HLA-C*70 antigen; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011993:Recombinant Fusion Proteins; D014966:Xanthenes; D001613:beta 2-Microglobulin; C034657:Texas red