Avian IgY binds to a monocyte receptor with IgG-like kinetics despite an IgE-like structure.
An ancestor of avian IgY was the evolutionary precursor of mammalian IgG and IgE, and present day chicken IgY performs the function of human IgG despite having the domain structure of human IgE. The kinetics of IgY binding to its receptor on a chicken monocyte cell line, MQ-NCSU, were measured, the first time that the binding of a non-mammalian antibody to a non-mammalian cell has been investigated (k(+1) = 1.14 +/- 0.46 x 10(5) mol(-1)sec(-1), k(-1) = 2.30 +/- 0.14 x 10(-3) s(-1), and K(a) = 4.95 x 10(7) m(-1)). This is a lower affinity than that recorded for mammalian IgE-high affinity receptor interactions (Ka approximately 10(10) m(-1)) but is within the range of mammalian IgG-high affinity receptor interactions (human: Ka approximately 10(8)-10(9) m(-1) mouse: Ka approximately 10(7)-10(8) m(-1). IgE has an extra pair of immunoglobulin domains when compared with IgG. Their presence reduces the dissociation rate of IgE from its receptor 20-fold, thus contributing to the high affinity of IgE. To assess the effect of the equivalent domains on the kinetics of IgY binding, IgY-Fc fragments with and without this domain were cloned and expressed in mammalian cells. In contrast to IgE, their presence in IgY has little effect on the association rate and no effect on dissociation. Whatever the function of this extra domain pair in avian IgY, it has persisted for at least 310 million years and has been co-opted in mammalian IgE to generate a uniquely slow dissociation rate and high affinity.
Taylor
Alexander I
AI
Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom.
Gould
Hannah J
HJ
Sutton
Brian J
BJ
Calvert
Rosaleen A
RA
D000818:Animals; D002645:Chickens; D016000:Cluster Analysis; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry*; D007136:Immunoglobulins / Q000737:chemistry*; D007438:Introns; D007700:Kinetics; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013045:Species Specificity
C016512:IgY; D007074:Immunoglobulin G; D007136:Immunoglobulins; D007073:Immunoglobulin E