title: A rapid and efficient strategy to generate allele-specific anti-HLA monoclonal antibodies.
abstract: That generation of allele-specific anti-human leukocyte antigen (HLA) monoclonal antibodies (ASHmAb) is very difficult is well known. This is thought to be due to the unique epitope structure, an assemblage of amino acid residues that lie separately in the amino acid sequence of human HLA, and to its low antigenicity compared with that of common epitopes recognized as xenogeneic determinants by mice. Here we report a rapid and efficient strategy to generate ASHmAb. Different from usual immunization methods is that we suppressed the production of non-allele-specific anti-HLA antibodies against xenogeneic determinants of HLA molecules by immunizing human HLA-B51 transgenic mice against non-HLA-B51 HLA tetramers. In addition, HLA-coated beads enabled rapid and efficient screening for ASHmAb. ASHmAb generated by this strategy will be useful for HLA typing and for clinical diagnosis, such as flow cytometry-based chimerism analysis for early detection of graft failure and relapse of leukemia after HLA-mismatched hematopoietic stem cell transplantation.
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Nao
authors.initials: N
authors.lastname: Suzuki
authors.forename: Tsuneyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ishii
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000302:isolation & purification; D000918:Antibody Specificity; D002459:Cell Fusion; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D059949:HLA-B51 Antigen; D006801:Humans; D006825:Hybridomas / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015235:HLA-B Antigens; D059949:HLA-B51 Antigen