The inhibitory receptor LIR-1 uses a common binding interaction to recognize class I MHC molecules and the viral homolog UL18.
LIR-1 is a class I MHC receptor related to natural killer inhibitory receptors (KIRs). Binding of LIR-1 or KIRs to class I molecules results in inhibitory signals. Unlike individual KIRs, LIR-1 recognizes many class I alleles and also binds UL18, a human cytomegalovirus class I MHC homolog. Here, we show that LIR-1 interacts with the relatively nonpolymorphic alpha3 domain of class I proteins and the analogous region of UL18 using its N-terminal immunoglobulin-like domain. The >1000-fold higher affinity of LIR-1 for UL18 than for class I illustrates how a viral protein competes with host proteins to subvert the host immune response. LIR-1 recognition of class I molecules resembles the CD4-class II MHC interaction more than the KIR-class I interaction, implying a functional distinction between LIR-1 and KIRs.
Chapman
T L
TL
Graduate Option in Biochemistry, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
Heikeman
A P
AP
Bjorkman
P J
PJ
D000483:Alleles; D000818:Animals; D015703:Antigens, CD; D016466:CHO Cells; D002213:Capsid / Q000737:chemistry / Q000378:metabolism*; D036022:Capsid Proteins; D006224:Cricetinae; D003412:Cricetulus; D003587:Cytomegalovirus / Q000276:immunology; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D008958:Models, Molecular; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000145:classification* / Q000378:metabolism*; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012995:Solubility; D014162:Transfection; D001613:beta 2-Microglobulin / Q000378:metabolism
D015703:Antigens, CD; D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins; C079750:VP23 protein, Human herpesvirus 1; D001613:beta 2-Microglobulin