title: Clinical and immunological significance of HLA-E in stem cell transplantation and cancer.
abstract: Human leukocyte antigen-E (HLA-E) is a nonclassical HLA class I molecule that canonically binds peptides derived from the leader sequence of classical HLA class I. HLA-E can also bind peptides from stress protein [e.g. heat shock protein 60 (Hsp60)] and pathogens, illustrating the importance of HLA-E for anti-viral and anti-tumor immunity. Like classical HLA class I molecules, HLA-E is ubiquitously expressed, however, it is characterized by only a very limited sequence variability and two dominant protein forms have been described (HLA-E*01:01 and HLA-E*01:03). HLA-E influences both the innate and the adaptive arms of the immune system by the engagement of inhibitory (e.g. NKG2A) and activating receptors [e.g. αβ T cell receptor (αβTCR) or NKG2C] on NK cells and CD8 T cells. The effects of HLA-E on the cellular immune response are therefore complex and not completely understood yet. Here, we aim to provide an overview of the immunological and clinical relevance of HLA-E and HLA-E polymorphism in stem cell transplantation and in cancer. We review novel insights in the mechanism via which HLA-E expression levels are controlled and how the cellular immune response in transplantation and cancer is influenced by HLA-E.
authors.affiliation: Department of Transplantation Immunology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Wieten
authors.forename: N M
authors.initials: NM
authors.lastname: Mahaweni
authors.forename: C E M
authors.initials: CE
authors.lastname: Voorter
authors.forename: G M J
authors.initials: GM
authors.lastname: Bos
authors.forename: M G J
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D033581:Stem Cell Transplantation; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000097625:HLA-E Antigens; C527059:KLRC2 protein, human
keywords: NK Natural killer cell; T cell; antigen presentation; cancer; human leukocyte antigen-E; immune response; stem cell transplantation