Rhesus macaque inhibitory and activating KIR3D interact with Mamu-A-encoded ligands.
Specific interactions between killer cell Ig-like receptors (KIRs) and MHC class I ligands have not been described in rhesus macaques despite their importance in biomedical research. Using KIR-Fc fusion proteins, we detected specific interactions for three inhibitory KIRs (3DLW03, 3DL05, 3DL11) and one activating KIR (3DS05). As ligands we identified Macaca mulatta MHC (Mamu)-A1- and Mamu-A3-encoded allotypes, among them Mamu-A1*001:01, which is well known for association with slow progression to AIDS in the rhesus macaque experimental SIV infection model. Interactions with Mamu-B or Mamu-I molecules were not found. KIR3DLW03 and KIR3DL05 differ in their binding sites to their shared ligand Mamu-A1*001:01, with 3DLW03 depending on presence of the α1 domain, whereas 3DL05 depends on both the α1 and α2 domains. Fine-mapping studies revealed that binding of KIR3DLW03 is influenced by presence of the complete Bw4 epitope (positions 77, 80-83), whereas that of KIR3DL05 is mainly influenced by amino acid position 77 of Bw4 and positions 80-83 of Bw6. Our findings allowed the successful prediction of a further ligand of KIR3DL05, Mamu-A1*002:01. These functional differences of rhesus macaque KIR3DL molecules are in line with the known genetic diversification of lineage II KIRs in macaques.
Primate Genetics Laboratory, German Primate Center-Leibniz Institute for Primate Research, 37077 Göttingen, Germany.
Cornelia
C
Rosner
Philip H
PH
Kruse
Meike
M
Hermes
Nicole
N
Otto
Lutz
L
Walter
D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D057809:HEK293 Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D008024:Ligands; D008253:Macaca mulatta; D025941:Protein Interaction Mapping; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054349:Receptors, KIR3DS1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; C110764:Mamu-A 01 antigen; C092249:Mamu-B 01 antigen, Macaca mulatta; C404270:Mamu-I antigen; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1; D011993:Recombinant Fusion Proteins