Allo-HLA reactivity of virus-specific memory T cells is common.
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.
Amir
Avital L
AL
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
D'Orsogna
Lloyd J A
LJ
Roelen
Dave L
DL
van Loenen
Marleen M
MM
Hagedoorn
Renate S
RS
de Boer
Renate
R
van der Hoorn
Menno A W G
MA
Kester
Michel G D
MG
Doxiadis
Ilias I N
II
Falkenburg
J H Frederik
JH
Claas
Frans H J
FH
Heemskerk
Mirjam H M
MH
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*
D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell