title: Recombinant antibodies encoded by IGHV1-69 react with pUL32, a phosphoprotein of cytomegalovirus and B-cell superantigen.
abstract: Leukemia cells from patients with chronic lymphocytic leukemia (CLL) express a highly restricted immunoglobulin heavy variable chain (IGHV) repertoire, suggesting that a limited set of antigens reacts with leukemic cells. Here, we evaluated the reactivity of a panel of different CLL recombinant antibodies (rAbs) encoded by the most commonly expressed IGHV genes with a panel of selected viral and bacterial pathogens. Six different CLL rAbs encoded by IGHV1-69 or IGHV3-21, but not a CLL rAb encoded by IGHV4-39 genes, reacted with a single protein of human cytomegalovirus (CMV). The CMV protein was identified as the large structural phosphoprotein pUL32. In contrast, none of the CLL rAbs bound to any other structure of CMV, adenovirus serotype 2, Salmonella enterica serovar Typhimurium, or of cells used for propagation of these microorganisms. Monoclonal antibodies or humanized rAbs of irrelevant specificity to pUL32 did not react with any of the proteins present in the different lysates. Still, rAbs encoded by a germ line IGHV1-69 51p1 allele from CMV-seropositive and -negative adults also reacted with pUL32. The observed reactivity of multiple different CLL rAbs and natural antibodies from CMV-seronegative adults with pUL32 is consistent with the properties of a superantigen.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Steininger
authors.forename: George F
authors.initials: GF
authors.lastname: Widhopf
authors.forename: Emanuela M
authors.initials: EM
authors.lastname: Ghia
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Morello
authors.forename: Katrina
authors.initials: K
authors.lastname: Vanura
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sanders
authors.forename: Deborah
authors.initials: D
authors.lastname: Spector
authors.forename: Don
authors.initials: D
authors.lastname: Guiney
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jäger
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D010750:Phosphoproteins; D011994:Recombinant Proteins; D018089:Superantigens; D014764:Viral Proteins