MISSING T-CELL RECEPTOR V-BETA FAMILIES FOLLOWING BLOOD-TRANSFUSION - THE ROLE OF HLA IN DEVELOPMENT OF IMMUNIZATION AND TOLERANCE

Previously, we showed that donor-specific CTL nonresponsiveness occurs in transfused recipients sharing one HLA haplotype (or at least one HLA-B and one HLA-DR antigen) with the blood donor. The aim of the present study was to disclose the distinct effects of BT on the T-cell receptor repertoire and to analyze which factors determine the tolerizing versus immunizing properties of BT. We show here that recipients of HLA-sharing BT develop not only donor-specific CTL nonresponsiveness posttransfusion, but also a significant decrease in the usage of one to three V beta families as shown by PCR. In contrast, recipients of non-HLA-sharing BT remained donor-specific CTL responders and did not decrease the usage of V beta families. In addition, these patients generated high-affinity CTL for donor antigens which could not be blocked by anti-CD8 mAb. Our results show that major alterations occur in the CTL and TCR V beta repertoire following BT. We hypothesize that the fate of transfused allogeneic lymphocytes in the host is based on the degree of sharing of HLA antigens with the host. This relationship determines the ultimate outcome of BT: immunization versus tolerization.