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 transp lantation. Some of these mHag are restricted to hemopoietic cells, oth ers show a broad tissue expression. Therefore, antileukemia reactivity is often associated with graft-vs-host disease. Here, we report the i dentification of a B cell leukemia-associated mHag, HB-1, recognized b y a CD8(+) CTL clone derived from peripheral blood of an acute lymphob lastic B cell leukemia patient who has been treated by HLA-matched bon e marrow transplantation. Interestingly, the CTL clone that recognizes HB-1 exhibits specific cytotoxicity toward leukemic as well as EBV-tr ansformed B cells, but not against untransformed B cells. Moreover, th e 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 B4402 and B*4403) and that 28% of HLA-B44-positive individuals e xpress HB-1. These findings demonstrate that leukemia-associated mHag with a restricted tissue distribution, such as HB-1, elicit CTL reacti vity in vivo. These Ags are of potential use in immunotherapy against leukemia because they generate antileukemia reactivity that is not ass ociated with graft-vs-host disease.