title: LILRA3 binds both classical and non-classical HLA class I molecules but with reduced affinities compared to LILRB1/LILRB2: structural evidence.
abstract: Structurally, Group 1 LILR (Leukocyte Immunoglobulin (Ig)-Like Receptor, also known as Ig-like transcripts, ILT; Leukocyte Ig-like receptor, LIR; and CD85) members are very similar in terms of the HLAIs (human leukocyte antigen class I molecules) binding region and were hypothesized that they all bind to HLAIs. As one of the Group 1 LILRs, LILRA3 is the only secretory LILR and may greatly control the inhibitory immune response induced by LILRB1, LILRB2, and other HLA-binding LILR molecules like LILRA1. Nevertheless, little was known about the binding of LILRA3 to HLAIs. In this report, we present the crystal structure of the LILRA3 domain 1 (D1) and evaluate the D1 and D1D2 (domain 1 and domain 2) binding to classical and non-classical HLAIs using BIAcore® surface plasmon resonance analysis (SPR). We found that LILRA3 binds both classical HLA-A*0201 and non-classical HLA-G1 but with reduced affinities compared to either LILRB1 or LILRB2. The polymorphic amino acids and the LILRA3 D1 structure support this notion.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Myongchol
authors.initials: M
authors.lastname: Ryu
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Gol
authors.initials: G
authors.lastname: Nam
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry*; D018360:Crystallography, X-Ray / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007107:Immune System; D007700:Kinetics; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C530062:LILRA3 protein, human; C105299:LILRB1 protein, human; C491341:LILRB2 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic