A novel minor histocompatibility antigen recognized by HLA-A31 restricted cytotoxic T lymphocytes generated from HLA-identical bone marrow donor lymphocytes.
Bulk cytotoxic T lymphocytes (CTL) were generated by in vitro stimulation of BMT donor lymphocytes with Philadelphia chromosome (Ph)-positive leukemic cells from an HLA-identical sibling patient. CTL were cytotoxic against the patient's leukemic cells as well as the EBV-lymphoblastoid cell line (EBV-LCL) generated from the patient's cells, suggesting that they recognize a minor histocompatibility antigen (mHAg). Subsequently, several CTL lines were established by a limiting dilution method and analyzed. One of these CTL lines, 16C12 CTL which used a single TCRbetaV3S1 for CD8 cells, lysed HLA-A31-positive leukemic cells and EBV-LCL, but not fibroblasts. The cytotoxicity against the patient's leukemic cells and EBV-LCL was blocked by anti-HLA-A31 moAb, anti-HLA-class I moAb, and anti-CD8 moAb, suggesting that this mHAg was presented with HLA-A31. The antigen recognized by 16C12 CTL seemed to be a novel mHAg, since HLA-A31 restricted antigen has not been reported to date and 16C12 CTL showed no cytotoxicity against EBV-LCL which probably express known mHAgs. CTL detecting this mHAg may play an important role in the GVL effect in HLA-A31-positive BMT patients.
Yazaki
M
M
Department of Pediatrics, Nagoya City University Medical School, Nagoya, Japan.
Takahashi
T
T
Andho
M
M
Akatsuka
Y
Y
Ito
T
T
Miyake
Y
Y
Ito
Y
Y
Nakamura
S
S
Wada
Y
Y
D016026:Bone Marrow Transplantation; D002648:Child; D003602:Cytotoxicity, Immunologic; D005260:Female; D020350:Graft vs Tumor Effect / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy*; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous
D015234:HLA-A Antigens; C069527:HLA-A31 antigen; D015778:Minor Histocompatibility Antigens