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) chromosomal translocation resulting in the expression of a novel bcr-abl fusion protein. The region spanning the fusion point is novel to the immune system and hence represents a potential leukemia-specific antigen. The ability of a 21-mer b3a2 fusion peptide to induce an in vitro lymphoproliferative response in a panel of 54 normal donors has been tested. 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 that of the control peptides was 1.80 (95% CI 1.63-1.97; p < 0.001). Responses were optimal at concentrations ranging from 0.3-150 micrograms/mL and in most cases peaked at 9 days. There was no clear relationship between level of responsiveness to the b3a2 fusion peptide and the presence of any single HLA-A, -B, -DR, or -DQ allele. HIA-DRB1*0404 was the only allele that was not associated with responsiveness. It is therefore likely that the b3a2 fusion peptide can be presented to T cells during a primary immune response in the context of several different class II HLA allelic products, albeit at low efficiency. The implications for specific active immunotherapy of CML patients are discussed.
MacIntyre
A R
AR
Department of Immunology, University of Liverpool, UK.
Christmas
S E
SE
Clark
R E
RE
D000483:Alleles; D000595:Amino Acid Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016044:Fusion Proteins, bcr-abl / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008969:Molecular Sequence Data
D000949:Histocompatibility Antigens Class II; D016044:Fusion Proteins, bcr-abl