Interaction of the LILRB1 inhibitory receptor with HLA class Ia dimers.
Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) has been reported to interact with a wide spectrum of HLA class I (HLA-I) molecules, albeit with different affinities determined by allelic polymorphisms and conformational features. HLA-G dimerization and the presence of intracellular Cys residues in HLA-B7 have been shown to be critical for their recognition by LILRB1. We hypothesized that dimerization of classical HLA class Ia molecules, previously detected in exosomes, might enhance their interaction with LILRB1. A soluble LILRB1-Fc fusion protein and a sensitive cellular reporter system expressing a LILRB1-ζ chimera were employed to assess receptor interaction with different HLA class Ia molecules transfected in the human lymphoblastoid 721.221 cell line. Under these conditions, intracellular Cys residues and HLA-I dimerization appeared associated with increased LILRB1 recognition. On the other hand, a marginal interaction of LILRB1 with primary monocytic cells, irrespective of their high HLA-I expression, was enhanced by type I interferon (IFN). This effect appeared disproportionate to the cytokine-induced increase of surface HLA-I expression and was accompanied by detection of HLA class Ia dimers. Altogether, the results support that a regulated assembly of these noncanonical HLA-I conformers during the immune response may enhance the avidity of their interaction with LILRB1.
Immunology Unit, University Pompeu Fabra, Barcelona, Spain.
Diogo
D
Baía
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Jordi
J
Pou
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
Des
D
Jones
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ofer
O
Mandelboim
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
John
J
Trowsdale
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Aura
A
Muntasell
Immunology Unit, University Pompeu Fabra, Barcelona, Spain.|Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Miguel
M
López-Botet
D000483:Alleles; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D015870:Gene Expression; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015793:HLA-B7 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D011971:Receptors, Immunologic / Q000378:metabolism*
D015703:Antigens, CD; D015234:HLA-A Antigens; D015793:HLA-B7 Antigen; D007370:Interferon Type I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic
HLA class I dimers; LILRB1; Macrophages; Type-I interferon