Bw4-reactive and Bw6-reactive antibodies recognize multiple distinct HLA structures that partially overlap in the α-1 helix

Charles T. Lutz, Kelly D. Smith, Nancy S. Greazel, Brian E. Mace, Dexter A. Jensen, Jane A. McCutcheon, Nancy E. Goeken

Research output: Contribution to journalArticlepeer-review

Abstract

Bw4 and Bw6 epitopes are expressed by mutually exclusive sets of HLA-B alleles and some HLA-A and HLA-C alleles. To test whether antithetical structures are required to express Bw4 and Bw6 epitopes, we measured binding of Bw4-reactive and Bw6-reactive alloantibodies and mAbs to HLA-B7 variants. A triple substitution of HLA-B7 α-1 helix residues 80, 82, and 83 created Bw4 and destroyed Bw6 epitopes detected by alloantibodies and mAbs. Both Bw4- reactive and Bw6-reactive mAbs competed for binding to HLA-B7 variants with single substitutions at residues 82 and 83. Substitutions of residues H93 and D119 which form a salt bridge in HLA-A2 also permitted binding by both Bw4- reactive and Bw6-reactive mAbs, suggesting that Bw4 and Bw6 epitopes are conformationally dependent. Six Bw4-reactive mAbs showed four distinct patterns of binding to HLA-B7 variants. Detailed analysis of 74 HLA-B7 single-residue variants showed that Bw6-reactive SFR8-B6 binding was prohibited by mutations altering the distal end of the α-1 helix and the nearby connecting loop. In contrast, Bw6-reactive BB7.6 binding required both α-1 and α-2 helix residues. Thus, Bw4-reactive and Bw6-reactive Abs recognize multiple distinct HLA structures that partially overlap in the α- 1 helix. As both Bw4 and Bw6 epitopes are expressed by some HLA-B7 variants, mutually exclusive expression of Bw4 and Bw6 epitopes in naturally occurring HLA class I molecules may reflect evolutionary pressure.

Original languageEnglish (US)
Pages (from-to)4099-4110
Number of pages12
JournalJournal of Immunology
Volume153
Issue number9
StatePublished - Nov 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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