Recognition of a B cell leukemia-associated minor histocompatibility antigen by CTL.
CTL directed against minor histocompatibility Ags (mHag) play a major role in antileukemia reactivity after HLA-identical bone marrow transplantation. Some of these mHag are restricted to hemopoietic cells, others show a broad tissue expression. Therefore, antileukemia reactivity is often associated with graft-vs-host disease. Here, we report the identification of a B cell leukemia-associated mHag, HB-1, recognized by a CD8+ CTL clone derived from peripheral blood of an acute lymphoblastic B cell leukemia patient who has been treated by HLA-matched bone marrow transplantation. Interestingly, the CTL clone that recognizes HB-1 exhibits specific cytotoxicity toward leukemic as well as EBV-transformed B cells, but not against untransformed B cells. Moreover, the CTL clone does not lyse PHA-stimulated T cell blasts, monocytes, and fibroblasts, indicating that HB-1 is mainly expressed by transformed B cells. Further analysis reveals that HB-1 is restricted by HLA-B44 (both B*4402 and B*4403) and that 28% of HLA-B44-positive individuals express HB-1. These findings demonstrate that leukemia-associated mHag with a restricted tissue distribution, such as HB-1, elicit CTL reactivity in vivo. These Ags are of potential use in immunotherapy against leukemia because they generate antileukemia reactivity that is not associated with graft-vs-host disease.
Dolstra
H
H
Department of Hematology, University Hospital Nijmegen, The Netherlands.
Fredrix
H
H
Preijers
F
F
Goulmy
E
E
Figdor
C G
CG
de Witte
T M
TM
van de Wiel-van Kemenade
E
E
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D015235:HLA-B Antigens / Q000235:genetics; D059948:HLA-B44 Antigen; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology*; D009928:Organ Specificity / Q000276:immunology; D010375:Pedigree; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D015778:Minor Histocompatibility Antigens