Characterizing monoclonal antibodies to antigenic domains of TCblR/CD320, the receptor for cellular uptake of transcobalamin-bound cobalamin.
Monoclonal antibodies (mAbs) were generated to the extracellular domain of transcobalamin receptor (TCblR) and used to identify the regions of the receptor protein involved in antibody binding. Based on the effect of transcobalamin bound cobalamin (TC-Cbl) on antibody binding, this study identified both blocking and binding antibodies. Both types of antibodies bind apo as well as holo receptors, whereas the blocking antibody when bound to the apo receptor prevents the binding and cellular uptake of TC-Cbl. Binding of these antibodies to truncated receptor constructs has identified the peptide domains of the receptor involved in antibody binding. These antibodies have potential utility in blocking cellular uptake of Cbl and delivery of drugs via TCblR, which is over-expressed in many cancers.
Jiang
Wenxia
W
School of Graduate Studies, SUNY-Downstate Medical Center, Brooklyn, NY 11203, USA.
Nakayama
Yasumi
Y
Sequeira
Jeffrey M
JM
Quadros
Edward V
EV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D001692:Biological Transport; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D014155:Transcobalamins / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014805:Vitamin B 12 / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C538894:CD320 protein, human; D011956:Receptors, Cell Surface; D014155:Transcobalamins; C028176:transcobalamin receptor; D014805:Vitamin B 12