Specific recognition of the viral protein UL18 by CD85j/LIR-1/ILT2 on CD8+ T cells mediates the non-MHC-restricted lysis of human cytomegalovirus-infected cells.
Immune evasion mechanisms of human CMV are known; however, the immune control of infection remains poorly elucidated. We show that interaction between the viral protein UL18 on infected cells and the invariant receptor CD85j/LIR-1/ILT2 expressed on CTL is relevant for the control of infection. Resting and activated CD8(+) T cells lysed UL18 expressing cells, whereas cells infected with CMV defective for UL18 were not killed. Lysis was not dependent on CD8(+) T cell Ag specificity, MHC-unrestricted and specifically blocked by anti-CD85j and anti-UL18 mAb. Moreover, soluble recombinant UL18Fc immunoprecipitated CD85j from T cells. Activation is mediated by CD85j and its pathway is unrelated to CD3/TCR engagement. UL18 is detected in immunocompromised patients with productive infection and the mechanism used in vivo by human CMV to ensure survival of the immunocompetent host may be mediated by activation signals delivered by infected cells to T lymphocytes via UL18/CD85j interactions.
Saverino
Daniele
D
Human Anatomy Section, Department of Experimental Medicine, University of Genova, Genoa, Italy.
Ghiotto
Fabio
F
Merlo
Andrea
A
Bruno
Silvia
S
Battini
Lorenzo
L
Occhino
Marzia
M
Maffei
Massimo
M
Tenca
Claudya
C
Pileri
Stefano
S
Baldi
Lucia
L
Fabbi
Marina
M
Bachi
Angela
A
De Santanna
Amleto
A
Grossi
Carlo E
CE
Ciccone
Ermanno
E
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D036022:Capsid Proteins / Q000096:biosynthesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007399:Interphase / Q000276:immunology; D019169:Jurkat Cells; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology
D015703:Antigens, CD; D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; C079750:VP23 protein, Human herpesvirus 1