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Publication Abstract from PubMed

Polyclonal autoantibodies against human granulocyte macrophage- colony stimulating factor (hGM-CSF) are a hallmark of pulmonary alveolar proteinosis (PAP) affection and several other reported autoimmune diseases. MB007 is a high affinity anti-human GM-CSF autoantibody isolated from a patient suffering from PAP which shows only modest neutralization of GM-CSF bioactivity. We describe the first crystal structure of a cytokine directed human IgG1lambda autoantibody binding fragment (Fab) at 1.9 A resolution. Its CDR3-H substantially differs from all previously reported VH7 germline IgG1 structures. We derive a reliable model of the antigen:autoantibody complex by using NMR chemical shift perturbation data in combination with computational methods. Superposition of the modeled complex structure with the human GM-CSF/GM-CSF ternary receptor complex reveals only little overlap between receptor and Fab when bound to GM-CSF. Our model provides a structural basis for understanding the mode-of-action of the MB007 autoantibody.

Molecular structure of human GM-CSF in complex with a disease-associated anti-human GM-CSF autoantibody and its potential biological implications.,Blech M, Seeliger D, Kistler B, Bauer MM, Hafner M, Horer S, Zeeb M, Nar H, Park JE Biochem J. 2012 Jul 27. PMID:22839360^[1]

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