Epstein-Barr virus infection abrogates the stimulatory capacity of B cells to a major histocompatibility complex class-II-restricted proliferative T-cell clone.
After BMT, donor T cells are activated which can display GvHD as well as GvL activities. In order to study this GvL-specific T-cell response in vitro, proliferative T-cell clones from post-BMT PBMCs were generated by stimulation with a patient's leukemic cells. One CD4+ T-cell clone (designated M-33) displayed strong proliferative activity against the patient's leukemic cells but not against the patient's EBV-LCLs. The induction of proliferation, however, appeared not to be leukemia specific. Detailed analysis of the reactivity patterns revealed that T-cell clone M-33 recognizes an as yet unknown nonpolymorphic determinant in the context of self HLA-DRw52, presented by all but one type of APC. T-cell clone M-33 proliferated upon stimulation by PB-MCs, freshly isolated B cells, monocytes, dendritic cells, leukemic B cells, and nonleukemic B-cell blasts; solely in vitro EBV-transformed B cells and in vivo EBV-infected B cells failed to induce proliferation of T-cell clone M-33. Neither surface expression of MHC or accessory molecules on the EBV cells nor suppression caused by the EBV-infected cells could explain their failure to stimulate T-cell clone M-33. We therefore hypothesize that the absence of the stimulatory capacity once the B cells are virally infected could be the result of competition for MHC class II binding of the Epstein-Barr viral peptides, thus affecting the postulated DRw52-restricted peptide for recognition by T-cell clone M-33.
van Lochem
E G
EG
Department of Immunohematology and Blood Bank, Leiden University Hospital, The Netherlands.
Bakker
A
A
Snijder
S
S
Aarts
M
M
de Gast
G C
GC
Goulmy
E
E
D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000821:virology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002472:Cell Transformation, Viral / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics; D006566:Herpesviridae Infections / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens