Genetic variability of the major histocompatibility complex class I homologue encoded by human cytomegalovirus leads to differential binding to the inhibitory receptor ILT2

Mar Valés-Gómez, Mitsunori Shiroishi, Katsumi Maenaka, Hugh T. Reyburn

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Human cytomegalovirus carries a gene, UL18, that is homologous to cellular major histocompatibility complex (MHC) class I genes. Like MHC class I molecules, the protein product of the UL18 gene associates with β2-microglobulin, and the stability of this complex depends on peptide loading. UL18 protein binds to ILT2 (CB85j), an inhibitory receptor present on B cells, monocytes, dendritic cells, T cells, and NK cells that also recognizes classical and nonclassical MHC molecules. These observations suggest that UL18 may play a role in viral immune evasion, but its real function is unclear. Since this molecule has similarity with polymorphic MHC proteins, we explored whether the UL18 gene varied between virus isolates. We report here that the UL18 gene varies significantly between virus isolates: amino acid substitutions were found in the predicted α1, α2, and α3 domains of the UL18 protein molecule. We also studied the ability of several variant UL18 proteins to bind to the ILT2 receptor. All of the variants tested bound to ILT2, but there were marked differences in the affinity of binding to this receptor. These differences were reflected in functional assays measuring inhibition of the cytotoxic capacity of NK cells via interaction with ILT2. In addition, the variants did not bind other members of the CD85 family. The implications of these data are discussed.

Original languageEnglish
Pages (from-to)2251-2260
Number of pages10
JournalJournal of virology
Volume79
Issue number4
DOIs
Publication statusPublished - Feb 1 2005

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Human herpesvirus 5
major histocompatibility complex
Major Histocompatibility Complex
Cytomegalovirus
genetic variation
receptors
Natural Killer Cells
natural killer cells
Proteins
genes
Genes
Viruses
MHC Class I Genes
Immune Evasion
proteins
Aptitude
immune evasion
Amino Acid Substitution
viruses
Cell Communication

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Genetic variability of the major histocompatibility complex class I homologue encoded by human cytomegalovirus leads to differential binding to the inhibitory receptor ILT2. / Valés-Gómez, Mar; Shiroishi, Mitsunori; Maenaka, Katsumi; Reyburn, Hugh T.

In: Journal of virology, Vol. 79, No. 4, 01.02.2005, p. 2251-2260.

Research output: Contribution to journalArticle

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