Multiple roles for the major histocompatibility complex class I-related receptor FcRn

Ghetie, Victor and Ward, E. Sally (2000) Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annual Review of Immunology, 18, 739-766. (doi:10.1146/annurev.immunol.18.1.739).

Abstract

Multiple functions have recently been identified for the neonatal Fc receptor FcRn. In addition, a human homolog of the rodent forms of FcRn has been identified and characterized. This major histocompatibility complex class I-related receptor plays a role in the passive delivery of immunoglobulin (Ig)Gs from mother to young and the regulation of serum IgG levels. In addition, FcRn expression in tissues such as liver, mammary gland, and adult intestine suggests that it may modulate IgG transport at these sites. These diverse functions are apparently brought about by the ability of FcRn to bind IgGs and transport them within and across cells. However, the molecular details as to how FcRn traffics within cells have yet to be fully understood, although in vitro systems have been developed for this purpose. The molecular nature of the FcRn-IgG interaction has been studied extensively and encompasses residues located at the CH2-CH3 domain interface of the Fc region of IgG. These Fc amino acids are highly conserved in rodents and man and interact with residues primarily located on the α2 domain of FcRn. Thus, it is now possible to engineer IgGs with altered affinities for FcRn, and this has relevance to the modulation of IgG serum half-life and maternofetal IgG transport for therapeutic applications.

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Contributors

Author: E. Sally Ward

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