THE INFLUENCE OF CLASS-II HLA TYPE ON THE LYMPHOPROLIFERATIVE RESPONSE OF NORMAL DONORS TO A BCR-ABL FUSION PEPTIDE

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) chrom osomal translocation resulting in the expression of a novel bcr-abl fu sion protein. The region spanning the fusion point is novel to the imm une system and hence represents a potential leukemia-specific antigen. The ability of a 21-mer b3a2 fusion peptide to induce an in vitro lym phoproliferative response in a panel of 54 normal donors has been test ed. This gave a mean stimulation index of 2.73 (95% CI 2.42-3.05) and 50/54 (93%) of donors gave responses that were greater than those with bcr or abl control peptides. The mean stimulation index relative to t hat of the control peptides was 1.80 (95% CI 1.63-1.97; p < 0.001). Re sponses were optimal at concentrations ranging from 0.3-150 mu g/mL an d in most cases peaked at 9 days. There was no clear relationship betw een level of responsiveness to the b3a2 fusion peptide and the presenc e of any single HLA-A, -B, -DR, or -DQ allele. HLA-DRB10404 was the o nly allele that was not associated with responsiveness. It is therefor e likely that the b3a2 fusion peptide can be presented to T cells duri ng a primary immune response in the context of several different class II HLA allelic products, albeit at low efficiency. The implications f or specific active immunotherapy of CML patients are discussed.