Generation of HLA-C-specific cytotoxic T cells in association with marrow graft rejection: Analysis of alloimmunity by T-cell cloning and testing of T-cell-receptor rearrangements

Peripheral blood mononuclear cells from a patient who rejected a T-cell-depleted marrow graft showed spontaneous cytotoxic activity specific for HLA-Cw4 and HLA-B35 alloantigens of the donor. T-cell-receptor complementarity-determining region 3 length distributions in a blood sample obtained at the time of rejection generally showed distortions in only 1 or 2 peaks, indicating that recipient T cells with a broad repertoire of antigen receptors survived the pretransplantation conditioning regimen. An HLA-Cw4-specific, CD8⁺ T-cell clone was recovered from a blood sample after rejection. The T-cell-receptor-B gene rearrangement expressed by this clone was not readily detectable in other blood samples drawn before or after the transplantation, indicating that this clone was only 1 of many recipient-derived T cells that recognized HLA alloantigens of the donor. These results demonstrate the role of the HLA-C locus in T-cell-mediated alloimmune responses and add to emerging evidence that indicates the need to evaluate HLA-C compatibility in selecting hematopoietic stem cell donors for patients who have an increased risk of rejection.