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

Daniele Saverino, Fabio Ghiotto, Andrea Merlo, Silvia Bruno, Lorenzo Battini, Marzia Occhino, Massimo Maffei, Claudya Tenca, Stefano Pileri, Lucia Baldi, Marina Fabbi, Angela Bachi, Amleto De Santanna, Carlo E. Grossi, Ermanno Ciccone

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)5629-5637
Number of pages9
JournalJournal of Immunology
Volume172
Issue number9
Publication statusPublished - May 1 2004

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Viral Proteins
Cytomegalovirus
T-Lymphocytes
Infection Control
T-Cell Antigen Receptor Specificity
Immune Evasion
Immunocompromised Host
Survival
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Saverino, D., Ghiotto, F., Merlo, A., Bruno, S., Battini, L., Occhino, M., ... Ciccone, E. (2004). 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. Journal of Immunology, 172(9), 5629-5637.

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. / Saverino, Daniele; Ghiotto, Fabio; Merlo, Andrea; Bruno, Silvia; Battini, Lorenzo; Occhino, Marzia; Maffei, Massimo; Tenca, Claudya; Pileri, Stefano; Baldi, Lucia; Fabbi, Marina; Bachi, Angela; De Santanna, Amleto; Grossi, Carlo E.; Ciccone, Ermanno.

In: Journal of Immunology, Vol. 172, No. 9, 01.05.2004, p. 5629-5637.

Research output: Contribution to journalArticle

Saverino, D, Ghiotto, F, Merlo, A, Bruno, S, Battini, L, Occhino, M, Maffei, M, Tenca, C, Pileri, S, Baldi, L, Fabbi, M, Bachi, A, De Santanna, A, Grossi, CE & Ciccone, E 2004, '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', Journal of Immunology, vol. 172, no. 9, pp. 5629-5637.
Saverino, Daniele ; Ghiotto, Fabio ; Merlo, Andrea ; Bruno, Silvia ; Battini, Lorenzo ; Occhino, Marzia ; Maffei, Massimo ; Tenca, Claudya ; Pileri, Stefano ; Baldi, Lucia ; Fabbi, Marina ; Bachi, Angela ; De Santanna, Amleto ; Grossi, Carlo E. ; Ciccone, Ermanno. / 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. In: Journal of Immunology. 2004 ; Vol. 172, No. 9. pp. 5629-5637.
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