Structural analysis of affinity maturation: The three-dimensional structures of complexes of an anti-nitrophenol antibody

Stacieann C. Yuhasz, Christian Parry, Mette Strand, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)1143-1155
Number of pages13
JournalMolecular Immunology
Volume32
Issue number14-15
DOIs
StatePublished - Oct 1995

Keywords

  • anti-nitrophenol monoclonal antibody
  • crystallographic structures affinity maturation

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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