title: Allo-HLA reactivity of virus-specific memory T cells is common.
abstract: Graft-versus-host disease and graft rejection are major complications of allogeneic HLA-mismatched stem cell transplantation or organ transplantation that are caused by alloreactive T cells. Because a range of acute viral infections have been linked to initiating these complications, we hypothesized that the cross-reactive potential of virus-specific memory T cells to allogeneic (allo) HLA molecules may be able to mediate these complications. To analyze the allo-HLA reactivity, T cells specific for Epstein-Barr virus, cytomegalovirus, varicella zoster virus, and influenza virus were tested against a panel of HLA-typed target cells, and target cells transduced with single HLA molecules. Eighty percent of T-cell lines and 45% of virus-specific T-cell clones were shown to cross-react against allo-HLA molecules. The cross-reactivity of the CD8 and CD4 T-cell clones was directed primarily against HLA class I and II, respectively. However, a restricted number of CD8 T cells exhibited cross-reactivity to HLA class II. T-cell receptor (TCR) gene transfer confirmed that allo-HLA reactivity and virus specificity were mediated via the same TCR. These results demonstrate that a substantial proportion of virus-specific T cells exert allo-HLA reactivity, which may have important clinical implications in transplantation settings as well as adoptive transfer of third-party virus-specific T cells.
authors.affiliation: Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Avital L
authors.initials: AL
authors.lastname: Amir
authors.forename: Lloyd J A
authors.initials: LJ
authors.lastname: D'Orsogna
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Marleen M
authors.initials: MM
authors.lastname: van Loenen
authors.forename: Renate S
authors.initials: RS
authors.lastname: Hagedoorn
authors.forename: Renate
authors.initials: R
authors.lastname: de Boer
authors.forename: Menno A W G
authors.initials: MA
authors.lastname: van der Hoorn
authors.forename: Michel G D
authors.initials: MG
authors.lastname: Kester
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
mesh_terms: D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014184:Transplantation, Homologous; D014780:Viruses / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell