TY - JOUR TI - The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition AU - Hsieh, Fu-Lien AU - Higgins, Matthew K A2 - Bjorkman, Pamela J VL - 6 PY - 2017 DA - 2017/05/20 SP - e27311 C1 - eLife 2017;6:e27311 DO - 10.7554/eLife.27311 UR - https://doi.org/10.7554/eLife.27311 AB - Antibodies are critical components of the human adaptive immune system, providing versatile scaffolds to display diverse antigen-binding surfaces. Nevertheless, most antibodies have similar architectures, with the variable immunoglobulin domains of the heavy and light chain each providing three hypervariable loops, which are varied to generate diversity. The recent identification of a novel class of antibody in humans from malaria endemic regions of Africa was therefore surprising as one hypervariable loop contains the entire collagen-binding domain of human LAIR1. Here, we present the structure of the Fab fragment of such an antibody. We show that its antigen-binding site has adopted an architecture that positions LAIR1, while itself being occluded. This therefore represents a novel means of antigen recognition, in which the Fab fragment of an antibody acts as an adaptor, linking a human protein insert with antigen-binding potential to the constant antibody regions which mediate immune cell recruitment. KW - antibody structure KW - LAIR1 KW - novel antigen recognition JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -