title: A class II-restricted cytotoxic T-cell clone recognizes a human minor histocompatibility antigen with a restricted tissue distribution.
abstract: Following a human leucocyte antigen (HLA)-identical allogeneic stem cell transplantation (allo-SCT), minor histocompatibility antigens (mHags) play an important role in the induction of graft-versus-leukaemia (GvL) and graft-versus-myeloma (GvM). Many mHags show ubiquitous tissue expression and are associated with GvL and graft-versus-host disease. Here we describe a cytotoxic CD4(+) T lymphocyte line and a cytotoxic, CD4(+) T cell clone (CTC), 3AB11, which recognized a tissue-restricted mHag. This CTC was isolated from a multiple myeloma patient with clinical GvM following an HLA-matched allo-SCT. CTC 3AB11 was activated in a HLA-DP*0401 restricted fashion and the antigen was expressed by 27% of HLA-DP*0401 positive Epstein-Barr virus (EBV)-transformed B-cell lines (EBV-B). Tissue distribution analysis of antigen 3AB11 showed it to be expressed by patient-derived EBV-transformed B cell lines (EBVp), the myeloma plasma cell-line UM9 and monocytes. It was weakly expressed by peripheral blood-derived phytohaemagglutinin-induced T-cell blasts and absent on CD40L stimulated peripheral B (CD40L B) cells and stromal cells. The relatively high prevalence of the HLA class II-restricted 3AB11 antigen, together with its apparent haematopoietic-restricted expression, makes it an antigen of interest for cellular immunotherapy.
authors.affiliation: Department of Haematology, UMCU, Heidelberglaan, Utrecht, The Netherlands.
authors.forename: Penny A
authors.initials: PA
authors.lastname: Holloway
authors.forename: Niels
authors.initials: N
authors.lastname: Kaldenhoven
authors.forename: Henriette M
authors.initials: HM
authors.lastname: Kok-Schoemaker
authors.forename: Mirjam van
authors.initials: Mv
authors.lastname: Dijk
authors.forename: Hennie G
authors.initials: HG
authors.lastname: Otten
authors.forename: Marcel
authors.initials: M
authors.lastname: Tilanus
authors.forename: Saskia
authors.initials: S
authors.lastname: Postma
authors.forename: Tuna
authors.initials: T
authors.lastname: Mutis
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
authors.forename: Andries C
authors.initials: AC
authors.lastname: Bloem
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D020350:Graft vs Tumor Effect; D004854:Herpesvirus 4, Human; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000032:analysis; D009101:Multiple Myeloma / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D014184:Transplantation, Homologous; D014775:Virus Activation
chemical_list: D000949:Histocompatibility Antigens Class II; D015778:Minor Histocompatibility Antigens