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Generation and characterization of CD1d‐specific single‐domain antibodies with distinct functional features
Author(s) -
Lameris Roeland,
Bruin Renée C. G.,
Bergen en Henegouwen Paul M. P.,
Verheul Henk M.,
Zweegman Sonja,
Gruijl Tanja D.,
Vliet Hans J.
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12635
Subject(s) - cd1d , biology , monoclonal antibody , epitope , clone (java method) , antibody , antigen , immunogenicity , microbiology and biotechnology , immune system , immunology , t cell , natural killer t cell , genetics , gene
Summary Ligation of the CD1d antigen‐presenting molecule by monoclonal antibodies (mAbs) can trigger important biological functions. For therapeutic purposes camelid‐derived variable domain of heavy‐chain‐only antibodies (VHH) have multiple advantages over mAbs because they are small, stable and have low immunogenicity. Here, we generated 21 human CD1d‐specific VHH by immunizing Lama glama and subsequent phage display. Two clones induced maturation of dendritic cells, one clone induced early apoptosis in CD1d‐expressing B lymphoblasts and multiple myeloma cells, and another clone blocked recognition of glycolipid‐loaded CD1d by CD1d‐restricted invariant natural killer T (iNKT) cells. In contrast to reported CD1d‐specific mAbs, these CD1d‐specific VHH have the unique characteristic that they induce specific and well‐defined biological effects. This feature, combined with the above‐indicated general advantages of VHH, make the CD1d‐specific VHH generated here unique and useful tools to exploit both CD1d ligation as well as disruption of CD1d–iNKT interactions in the treatment of cancer or inflammatory disorders.