HLA-E-restricted recognition of human cytomegalovirus by a subset of cytolytic T lymphocytes

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Abstract

Natural killer (NK)-cytotoxic T lymphocytes (CTL) are a subset of CD8 + cytolytic T lymphocytes that express human leukocyte antigen (HLA) class I-specific inhibitory receptors. They are detectable as monoclonal expansions in the blood of cytomegalovirus (CMV)-seropositive individuals displaying particular HLA-Cw allotypes. Similar to NK cells, they are capable of killing various allogeneic tumor cell lines, a function referred to as "NK-like activity." The mechanism underlying this unusual functional property has recently been clarified. Via their T-cell receptor, NK-CTL recognize the nonclassical HLA class I molecule HLA-E, which is characterized by a limited polymorphism and by the ability to bind peptides derived from the leader sequence of various HLA class I alleles as well as from few viral proteins. The analysis of the T-cell receptor avidity revealed that NK-CTL recognize with high avidity a CMV UL40-derived peptide. The HLA-E-restricted recognition of CMV by NK-CTL may represent an important immunologic strategy in defenses against this virus. Indeed, unlike conventional CTL, NK-CTL mediated lysis is apparently not affected by the downregulation of major histocompatibility complex class I that occurs during CMV infection. Because the CMV UL40-derived peptide is identical to the one generated from the leader sequence of various HLA-Cw alleles, NK-CTL are also able to display an "HLA-E-dependent alloreactivity" against allogeneic target cells expressing appropriate HLA-Cw alleles. This broad ability to recognize and kill allogeneic cells may pose serious problems in transplantation.

Original languageEnglish
Pages (from-to)437-445
Number of pages9
JournalHuman Immunology
Volume65
Issue number5
DOIs
Publication statusPublished - May 2004

Keywords

  • alloreactivity
  • cytomegalovirus
  • HLA-E
  • T cells
  • UL40

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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