Peripheral blood stem cell allograft rejection mediated by CD4+ T lymphocytes recognizing a single mismatch at HLA-DPβ1*0901

Abstract

Little is known about the molecular characteristics of alloantigens recognized by alloreactive T cells mediating hematologic stem cell graft rejection. In particular, it has never been shown that such alloantigens can be encoded by HLA-DPβ alleles. Indeed, matching for HLA-DP antigens is generally not considered to be of functional importance for the outcome of allogeneic bone marrow or peripheral blood stem cell transplantation. In this study, a case of peripheral blood stem cell allograft rejection was investigated in which the patient and donor differed for a single mismatch at HLA-DP in the rejection direction. Patient-derived T lymphocytes circulating at the time of rejection showed direct ex vivo cytotoxic activity against donor-derived B-lymphoblastoid cells as well as other HLA-DPβ1*0901–expressing targets. The presence of HLA-DPβ1*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-DPβ1*0901–expressing targets including donor B-lymphoblastoid cells were generated both by nonspecific and by donor-specific in vitro stimulation. Taken together, these data demonstrate that HLA-DP can be the target antigen of cytotoxic CD4+ T lymphocytes involved in peripheral blood stem cell allograft rejection.