3phq

Publication Abstract from PubMed

The structure of the antigen-binding fragment from the monoclonal antibody S64-4 in complex with a pentasaccharide bisphosphate fragment from chlamydial lipopolysaccharide has been determined by x-ray diffraction to 2.6 A resolution. Like the well-characterized antibody S25-2, S64-4 displays a pocket formed by the residues of germline sequence corresponding to the heavy and light chain V genes that binds the terminal Kdo residue of the antigen; however, while S64-4 shares the same heavy chain V gene as S25-2 it has a different light chain V gene. The new V(L) gene codes for a combining site that displays greater affinity, different specificity, and allows a novel antigen conformation that brings a greater number of antigen residues into the combining site than possible in S25-2. Further, while antibodies in the S25-2 family use CDR H3 to discriminate among antigens, S64-4 achieves its specificity via the new light chain V gene and resulting change in antigen conformation. These structures reveal an intriguing parallel strategy where two different combinations of germline-coded V genes can act as starting points for the generation of germline antibodies against chlamydial antigens, and shows how anti-carbohydrate antibodies can exploit the conformational flexibility of this class of antigens to achieve high affinity and specificity independently of CDR H3.

Structural insights into parallel strategies for germline antibody recognition of LPS from Chlamydia.,Evans DW, Muller-Loennies S, Brooks CL, Brade L, Kosma P, Brade H, Evans SV Glycobiology. 2011 May 4. PMID:21543444^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.