Cis association of leukocyte Ig-like receptor 1 with MHC class I modulates accessibility to antibodies and HCMV UL18.
Leukocyte Ig-like receptor (LIR) 1 (CD85j/ILT2/LILRB1) is an inhibitory receptor with broad specificity for MHC class I (MHC-I) and the human CMV MHC-I homologue UL18. LIR-1 can inhibit NK cells through the conventional interaction with MHC-I expressed on a target cell (in trans) but the nature and the effects of LIR-1 interactions with MHC-I in cis are not well understood. Here we show that MHC-I expressed in cis has an impact on the detection of LIR-1 with various antibodies. We found the cis interaction alters recognition by only one of two antibodies known to block functional trans recognition by LIR-1 on NK cells. Specifically, we observed an enhancement of recognition with GHI/75 in the presence of various MHC-I alleles on 721.221 cells. We found that blocking the LIR-1 contact site with anti-MHC-I antibodies decreased detection of LIR-1 with GHI/75. We also observed a decrease in GHI/75 following acid denaturation of MHC-I. Finally, disruption of LIR-1 cis interactions with MHC-I significantly enhanced UL18-Fc binding to NK92 cells and enhanced the relative inhibition of NK92 cells by HLA-G. These results have implications for LIR-1 function in scenarios such as infection when MHC-I levels on effector cells may be increased by IFNs.
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Nicholas L
NL
Li
Li
L
Fu
Hannes
H
Uchtenhagen
Adnane
A
Achour
Deborah N
DN
Burshtyn
D000906:Antibodies / Q000276:immunology / Q000378:metabolism*; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D036022:Capsid Proteins / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D019343:Citric Acid / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011485:Protein Binding; D011489:Protein Denaturation / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D015703:Antigens, CD; D036022:Capsid Proteins; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; C079750:VP23 protein, Human herpesvirus 1; D019343:Citric Acid