Specificity of two anti-class I HLA monoclonal antibodies that block class I recognition by the NKB1 killer cell inhibitory receptor
Abstract
Cytolysis by NK cells that possess the NKB1 killer cell inhibitory receptor is inhibited by target cell expression of Bw4+ HLA-B molecules. The inhibitory effect can be prevented by addition of mAbs which block recognition of class I molecules by NKB1. The epitopes recognized by two anti-class I mAbs, DX15 and DX16, which inhibit the interaction of NKB1 with class I have been characterized. Binding of DX15 and DX16 to class I allotypes was investigated by flow cytometric analysis of transfected cell lines which express just one HLA-A, B, or C allele, and by immunoprecipitation of class I molecules from HLA typed B-lymphoblastoid cell lines, followed by isoelectric focusing. The DX16 mAb recognizes class I allotypes which possess alanine at position 71 of the alpha 1 helix, and therefore has a specificity resembling that of the ME1 mAb but with broader specificity. Class I recognition by DX15 is affected by polymorphisms of the C-terminal part of the alpha 1 helix, and the N-terminal part of the alpha 2 helix. DX15 thus appears to recognize a complex epitope near the end of the peptide binding groove which may be conformationally determined. Both antibodies are as effective as the anti-NKB1 mAb (DX9) in preventing class I recogn...Continue Reading
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