Failure of Epstein‐Barr virus‐specific cytotoxic T lymphocytes to lyse B cells transformed with the B95‐8 strain is mapped to an epitope that associates with the HLA‐B8 antigen
There are two types, A and B, of Epstein‐Barr virus (EBV) and B95‐8 represents the common type A laboratory strain. Herein, we show in a family study that paternal EBV‐specific cytotoxic T lymphocytes (CTL) generated in short‐term cultures following stimulation with the autologous B95‐8‐transformed lymphoblastoid cell line (LCL) or B cells freshly infected with the B95‐8 isolate did not lyse haploidentical B95‐8 LCL expressing the HLA‐A1‐B8,‐DR3 paternal haplotype. In contrast, the haploidentical B95‐8 LCL expressing the HLA‐A11,‐B51,‐DR7 paternal haplotype was strongly lysed. Moreover, paternal CTL generated in response to stimulation with the B95‐8 LCL expressing the haploidentical HLA‐A1,‐B8, ‐DR3 paternal haplotype included an allogeneic response against the maternal haplotype but no EBV‐specific response as shown by the poor lysis of the autologous LCL target cells. However, stimulation with the haploidentical HLA‐A11,‐B51, ‐DR7 paternal haplotype resulted in the generation of both an allogeneic and an EBV‐specific response. CTL clones were generated from two HLA‐B8+ donors in response to stimulation with the autologous type A LCL transformed with wildtype EBV. The clones were cross‐reactive for an immunodominant B95‐8‐associalcd peptide epitope that interacted with the HLA‐B8 allele but failed to lyse B95‐8‐transformed LCL largets unless the targets were pre‐coated with the exogenous peptide. A CTL clone that was initially stimulated with the autologous BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA‐B8+ donor, but failed to lyse the B95‐8 LCL from that donor. The observed haplotype preference can be explained in terms of sequence variation between the B95‐8 and the corresponding wildtype epitope. Our findings may help to clarify the role of EBV in the pathogenesis of primary Sjögren's syndrome which is closely associated with HLA‐B8.