Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide.
HLA-B27 can form beta-2 microglobulin (beta2m)-associated heterotrimers (HLA-B27) and beta2m-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-gamma 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-gamma 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.
Kollnberger
Simon
S
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK. simon.kollnberger@imm.ox.ac.uk
Chan
Antoni
A
Sun
Mei-Yi
MY
Chen
Li Ye
LY
Wright
Cynthia
C
di Gleria
Kati
K
McMichael
Andrew
A
Bowness
Paul
P
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D015153:Blotting, Western; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015796:HLA-B27 Antigen / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D054347:Receptors, KIR3DL2; D025241:Spondylarthritis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000939:Epitopes; D015796:HLA-B27 Antigen; C515083:KIR3DL1 protein, human; C515084:KIR3DL2 protein, human; D010455:Peptides; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D054347:Receptors, KIR3DL2