Title : Crystal structure of B-cell co-receptor
CD19 in complex with antibody B43 reveals an unexpected fold
Abstract :
- CD19 is a transmembrane protein expressed on malignant B cells, but not in other lineages or other tissues, which makes it an attractive target for monoclonal antibody-mediated immunotherapy
- Anti- CD19 antibody B43 was utilized in a bispecific T-cell engager ( BiTE ) blinatumomab that demonstrated potency for the treatment of relapsed acute lymphoblastic leukemia
- To gain insight into the mechanism of action of the antibody, the crystal structure of B43 Fab was determined in complex with CD19 and in the unbound form
- The structure revealed the binding epitope , explained the lack of cross-reactivity toward non-human species, and suggested the key-and-lock mechanism of antigen recognition
- Most unexpectedly, the structure revealed a unique molecular topology of CD19
- Rather than a tandem of c-type immunoglobulin folds predicted from the amino acid sequence , the extracellular domain of CD19 exhibits an elongated β-sandwich formed by two immunoglobulin folds by swapping their C-terminal halves
- This is the first structure of CD19 , which has no sequence homologs