The Journal of Immunology, Vol 158, Issue 2 560-565, Copyright © 1997 by American Association of Immunologists

ARTICLES

Recognition of a B cell leukemia-associated minor histocompatibility antigen by CTL

H Dolstra, H Fredrix, F Preijers, E Goulmy, CG Figdor, TM de Witte and E van de Wiel-van Kemenade
Department of Hematology, University Hospital Nijmegen, The Netherlands.

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.

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