Specificity of two anti-class I HLA monoclonal antibodies that block class I recognition by the NKB1 killer cell inhibitory receptor.
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 recognition by the NKB1 receptor. DX16 also blocked recognition by a B*0702 allospecific CTL clone, whereas DX15 did not.
Gumperz
J E
JE
Department of Microbiology and Immunology, Stanford University, California, USA.
Paterson
J C
JC
Litwin
V
V
Valiante
N
N
Lanier
L L
LL
Parham
P
P
Little
A M
AM
D000409:Alanine / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D002461:Cell Line, Transformed; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D000409:Alanine