MULTIPLE MINOR HISTOCOMPATIBILITY ANTIGEN DISPARITIES BETWEEN A RECIPIENT AND 4 HLA-IDENTICAL POTENTIAL SIBLING DONORS FOR BONE-MARROW TRANSPLANTATION

A patient with acute leukemia and her family including four HLA-identi cal siblings were analyzed to select a donor who was not only HLA- but also minor histocompatibility (mH) antigen compatible for allogeneic bone marrow transplantation (BMT). The HLA-A2 restricted mH antigen-sp ecific HA-1, -2, -4, and -5 cytotoxic T-lymphocyte (CTL) clones were u sed to type the family members for expression of these mH antigens. Th e patient and one HLA-identical sibling were compatible for these mH a ntigens. This sibling was selected as the bone marrow donor. The patie nt engrafted promptly but developed acute and chronic graft-versus-hos t disease. To study the presence of other mH antigen disparities betwe en recipient and donor, host-versus-graft CTL lines and clones were ge nerated by stimulation of recipient peripheral blood lymphocytes (PBLs ) with donor bone marrow cells, and graft-versus-host CTL lines were g enerated after BMT by stimulation of PBLs of donor origin with recipie nt bone marrow cells. These CTL lines were cytotoxic to cells from the bone marrow donor and from the recipient, respectively, and to cells from several other family members. T-cell lines, generated from the pa tient after BMT by stimulation of recipient-derived PBLs with donor bo ne marrow cells, exhibited no specific cytotoxicity to donor or recipi ent cells. Chimerism studies after BMT revealed that the PBLs and T-ce ll lines generated after BMT were of donor origin. CTL lines that were generated from PBLs from the three other HLA-identical siblings in th is family by stimulation with HLA-identical donor bone marrow cells al so exhibited cytotoxicity to cells from several family members. Our re sults show that in addition to compatibility for HA-1, -2, -4, and -5 between the recipient and the donor, other mH antigen disparities exis ted between all HLA-identical siblings, illustrating the high degree o f polymorphism of mH antigens and therefore the difficulty of finding mH antigen-compatible donor-recipient pairs even when more than one HL A-identical sibling is present within a family.