Peripheral blood stem cell allograft rejection mediated by CD4(+) T lymphocytes recognizing a single mismatch at HLA-DP beta 1*0901

Little is known about the molecular characteristics of alloantigens recogni zed by alloreactive T cells mediating hematologic stem cell graft rejection . In particular, it has never been shown that such alloantigens can be enco ded by HLA-DP beta alleles. Indeed, matching for HLA-DP antigens is general ly not considered to be of functional importance for the outcome of allogen eic bone marrow or peripheral blood stem cell transplantation. In this stud y, a case of peripheral blood stem cell allograft rejection was investigate d in which the patient and donor differed for a single mismatch at HLA-DP i n the rejection direction. Patient-derived T lymphocytes circulating at the time of rejection showed direct ex vivo cytotoxic activity against donor-d erived B-lymphoblastoid cells as well as other HLA-DP beta1*0901-expressing targets. The presence of HLA-DP beta1*0901-specific effectors in vivo was further confirmed by in vitro stimulation experiments. CD4(+) T-cell lines and clones with specific cytotoxic activity against HLA-DP beta1*0901-expre ssing targets including donor B-lymphoblastoid cells were generated both by nonspecific and by donor-specific in vitro stimulation. Taken together, th ese data demonstrate that HLA-DP can be the target antigen of cytotoxic CD4 (+) T lymphocytes involved in peripheral blood stem cell allograft rejectio n.