Selective reactivation of Epstein-Barr virus-specific cytotoxic T cells by stimulation in vitro with allogeneic virus-transformed HLA-homozygous typing cells

Abstract

Epstein-Barr (EB) virus-specific cytotoxic T-cell preparations, produced by stimulation in vitro of peripheral blood lymphocytes with the autologous virus-transformed cell line, are HLA-A and B antigen-restricted and, with some donors, show preferetial restriction through one or two of the four relevant antigens of the donor's HLA type. It has now been demonstrated that such EB virus-specific cytotoxic T cells may also be reactivated by stimulation with allogeneic virus-transformed cells provided that there is no mismatch of the HLA-A and B antigens between the responder and stimulator cell donors. In particular, virus-transformed cell lines from HLA-homozygous donors HLA-A and B antigen-matched to one of the haplotypes of an HLA-heterozygous responder were shown to reactivate selectively only those EB virus-specific cytotoxic T cells restricted through the HLA-A and B antigens present on the allogeneic stimulating cells. In addition to confirming the polyclonal nature of the HLA-restricted EB virus-specific cytotoxic T-cell response, this new experimental procedure has allowed the production, and subsequent expansion as cell lines dependent upon T-cell growth factor, of those effector cells restricted through the “nonpreferred” HLA antigens that are poorly represented in the response induced by stimulation with autologous virus-transformed cells.