UNUSUAL UNIFORMITY OF THE N-LINKED OLIGOSACCHARIDES OF HLA-A, HLA-B, AND HLA-C GLYCOPROTEINS

MHC class I glycoproteins possess an invariant site for N-linked oligo saccharide 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 isol ated 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 pre dominant 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. Identic al oligosaccharides were present on different allotypes of a class I H LA locus, and in particular, HLA-C allotypes defining two inhibitory s pecificities for NK cells were shown to possess the same set of oligos accharides. The uniformity of oligosaccharide structure associated wit h different HLA-A, -B, and -C products and the relative lack of hetero geneity for any given allotype are unusual features for a mammalian gl ycoprotein. Particularly striking is that such conserved oligosacchari de structures juxtapose the major regions of amino acid sequence varia tion within the Ag recognition site, including the polymorphisms of th e alpha(1) helix that determine the inhibitory ligands for human NK ce lls.