POLYMORPHISM IN CD33 AND CD34 GENES - A SOURCE OF MINOR HISTOCOMPATIBILITY ANTIGENS ON HEMATOPOIETIC PROGENITOR CELLS

Following bone marrow stem cell transplantation allo-responses against haemopoietic progenitor cells (HPC), causing graft rejection and graf t-versus-leukaemia effects, can be induced by donor T cells recognizin g peptides derived from polymorphic endogenous proteins present in HPC , Since CD33 and CD34 are both expressed on HPC, we looked for genetic polymorphisms that might be the source of minor histocompatibility an tigens (mHA) on such cells. Bone marrow from 14 donors and their HLA-i dentical recipients undergoing BRIT for haematological malignancies we re studied. Using non-radioactive single-strand conformation polymorph ism analysis (cold SSCP) of complementary DNA encoding CD33 and CD34, three DNA polymorphisms, two in CD33 and one in CD34 were found and se quenced. Two were in non-coding regions, but in CD33, ATA or ATG at co don 183 resulted in an lie or Met in the protein sequence. Nonapeptide s derived from both alleles were predicted to bind to HLA A68.1. Thus two alleles of CD33 protein exist that could be mHA. With an alternate allele frequency of < 10%, allo-responses against CD33 would be uncom mon after marrow transplantation. However, donors homozygous for this allele could be used to generate cytotoxic T cells against the frequen t CD33 allele, for adoptive therapy of leukaemia.