Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide
Kollnberger S., Chan A., Sun MY., Chen LY., Wright C., di Gleria K., McMichael A., Bowness P.
HLA-B27 can form beta-2 microglobulin (β2m)-associated heterotrimers (HLA-B27) and β2m-free homodimers (B27 2 ). Here, we study the role of complexed peptide in the interaction of these forms of B27 with the killer cell immunoglobulin (Ig)-like receptors KIR3DL1 and KIR3DL2 and with Ig-like transcripts LILRB1 and LILRB2. HLA-B27 tetramers complexed with three of five different naturally processed self peptides and three of seven pathogen-derived epitopes bound to KIR3DL1-expressing transfectants and NK cells. Heterotrimeric complexes containing peptides with charged amino acids at position 8 did not bind to KIR3DL1; however, studies with analogue peptides demonstrated that these are not the only peptide residues involved in binding. KIR3DL1 ligation by HLA-B27 inhibited NK cell IFN-γ production in a peptide-dependent fashion. B27 but not HLA-A2, B7 or B57 heavy chains formed homodimers in the presence of peptide epitopes. B27 2 bound to KIR3DL1, KIR3DL2 and LILRB2 but not LILRB1. KIR3DL2 ligation by B27 2 inhibited NK and T cell IFN-γ production. By contrast with HLA heterotrimers, B27 2 binding to KIR did not depend on the sequence of the bound peptide. Differences in KIR binding to classical HLA and B27 2 could be involved in the pathogenesis of spondyloarthritis. © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.