Unusual uniformity of the N-linked oligosaccharides of HLA-A, -B, and -C glycoproteins.
MHC class I glycoproteins possess an invariant site for N-linked oligosaccharide addition at position 86 of the heavy chain. For human HLA-A, -B, and -C class I glycoproteins, position 86 is the only site of N-linked glycosylation. Comparison of the size and relative abundance of oligosaccharides associated with nine HLA-A, -B, or -C allotypes isolated from EBV-transformed B cell lines and mixtures of HLA-A, -B, and -C allotypes isolated from pooled PBLs revealed a very restricted set of structures. Allotypes encoded by the HLA-A and -B loci have two predominant glycan structures that were almost exclusively di-sialylated. In contrast, HLA-C allotypes have four glycan structures, comprising those associated with HLA-A and -B and two additional glycans. Identical oligosaccharides were present on different allotypes of a class I HLA locus, and in particular, HLA-C allotypes defining two inhibitory specificities for NK cells were shown to possess the same set of oligosaccharides. The uniformity of oligosaccharide structure associated with different HLA-A, -B, and -C products and the relative lack of heterogeneity for any given allotype are unusual features for a mammalian glycoprotein. Particularly striking is that such conserved oligosaccharide structures juxtapose the major regions of amino acid sequence variation within the Ag recognition site, including the polymorphisms of the alpha 1 helix that determine the inhibitory ligands for human NK cells.
Barber
L D
LD
Department of Structural Biology, Stanford University, CA 94305, USA.
Patel
T P
TP
Percival
L
L
Gumperz
J E
JE
Lanier
L L
LL
Phillips
J H
JH
Bigge
J C
JC
Wormwald
M R
MR
Parekh
R B
RB
Parham
P
P
D000328:Adult; D002240:Carbohydrate Sequence; D002461:Cell Line, Transformed; D003601:Cytotoxicity Tests, Immunologic; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology; D015234:HLA-A Antigens / Q000737:chemistry / Q000302:isolation & purification; D015235:HLA-B Antigens / Q000737:chemistry / Q000302:isolation & purification; D015236:HLA-C Antigens / Q000737:chemistry / Q000145:classification / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000276:immunology; D011110:Polymorphism, Genetic / Q000276:immunology
D006023:Glycoproteins; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D009844:Oligosaccharides