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.
Pei
J
J
Fred Hutchinson Cancer Research Center and the Department of Medicine, University of Washington, Seattle 98109-1024, USA.
Akatsuka
Y
Y
Anasetti
C
C
Lin
M T
MT
Petersdorf
E W
EW
Hansen
J A
JA
Martin
P J
PJ
D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D017809:Fatal Outcome; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007519:Isoantigens; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D015236:HLA-C Antigens; D007519:Isoantigens