Abstract
Affinity maturation of the immune response to nitrophenol-containing antigens has been extensively investigated. Significant strides made during the past several years with the advent of PCR technology have provided a wealth of biochemical knowledge. Structural investigations of the phenomena have however been limited. We have determined the three-dimensional structure of the Fab fragment of 88C6 12, an anti-4-hydroxy-3-nitrophenyl acetic acid antibody complexed with the immunizing hapten and with a heteroclitic iodinated hapten. The crystallographic structure of the complexes reveals that the binding is stabilized by a number of hydrogen bonds and extensive van der Waals interactions between the hapten and the antibody. In addition, the Fab binding pocket contains a region of positive electrostatic potential well suited for interaction with the predominant resonance form of the nitrophenyl ring system. The observed heteroclicity towards the iodinated hapten is not a direct result of iodine-protein interactions, but results from the enhanced stability in the iodinated ring of the resonance form that binds the antibody. In addition this investigation provides a rationale for the strong preference for the substitution in the heavy chain from the germline gene encoded Trp 33 to Leu 33 in the mature anti-nitrophenol response.
Original language | English (US) |
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Pages (from-to) | 1143-1155 |
Number of pages | 13 |
Journal | Molecular Immunology |
Volume | 32 |
Issue number | 14-15 |
DOIs | |
State | Published - Oct 1995 |
Keywords
- anti-nitrophenol monoclonal antibody
- crystallographic structures affinity maturation
ASJC Scopus subject areas
- Immunology
- Molecular Biology