Three-dimensional Structure of a Heteroclitic Antigen-antibody Cross-reaction Complex

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 Aug 15

PMID 8356074

Citations 25

Authors

V Chitarra

P M Alzari

G A Bentley

T N Bhat

J L Eisele

A Houdusse

J Lescar

H SOUCHON

R J POLJAK

Affiliations

Soon will be listed here.

Abstract

Although antibodies are highly specific, cross-reactions are frequently observed. To understand the molecular basis of this phenomenon, we studied the anti-hen egg lysozyme (HEL) monoclonal antibody (mAb) D11.15, which cross-reacts with several avian lysozymes, in some cases with a higher affinity (heteroclitic binding) than for HEL. We have determined the crystal structure of the Fv fragment of D11.15 complexed with pheasant egg lysozyme (PHL). In addition, we have determined the structure of PHL, Guinea fowl egg lysozyme, and Japanese quail egg lysozyme. Differences in the affinity of D11.15 for the lysozymes appear to result from sequence substitutions in these antigens at the interface with the antibody. More generally, cross-reactivity is seen to require a stereochemically permissive environment for the variant antigen residues at the antibody-antigen interface.

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