Selective apoptosis of neoplastic cells by the HLA-DR-specific monoclonal antibody.

The human major histocompatibility complex (MHC) class II molecule-specific monoclonal antibody (mAb) 8D1 can induce apoptosis of tumor cells expressing HLA-DR molecules on their surface. This effect is associated with a cross-linking of HLA-DR, since monovalent Fab fragments of 8D1 cannot mediate cytotoxicity unless they are anchored to a solid support. Anti-neoplastic activity of 8D1 is highly selective, i.e. the mAb affects neither the viability nor the function of non-malignant HLA-DR+ cells. These findings raise the possibility of a selective antibody-based anti-tumor therapy of class II positive blood cell neoplasm.

Peptide dependence of major histocompatibility complex class II specific alloreactive responses.

Splenic cells from transgenic mice, in which a single peptide is complexed to all major histocompatibility complex (MHC) class II molecules, are found to be incapable of triggering primary allogeneic mixed lymphocyte/leucocyte reactions (MLR) when co-cultured with lymphocytes from MHC class II congenic mouse strains. In addition, a single HLA-DR-blocking peptide can completely abrogate the capacity of splenocytes from chimeric HLA-DR/H2-E transgenic mice to stimulate primary MLR of T cells from wild-type mice. These results indicate that the primary alloreactive response is directed against a multitude of peptides presented by allogeneic MHC molecules.