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

Multiple functions have recently been identified for the neonatal Fc recept or 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 (I g)Gs from mother to young and the regulation of serum IgG levels. In additi on, FcRn expression in tissues such as liver, mammary gland, and adult inte stine suggests that it may modulate IgG transport at these sites. These div erse functions are apparently brought about by the ability of FcRn to bind IgGs and transport them within and across cells. However, the molecular det ails as to how FcRn traffics within cells have yet to be fully understood, although in vitro systems have been developed for this purpose. The molecul ar nature of the FcRn-IgG interaction has been studied extensively and enco mpasses residues located at the CH2-CH3 domain interface of the Fc region o f IgG. These Fc amino acids are highly conserved in rodents and man and int eract with residues primarily located on the alpha 2 domain of FcRn. Thus, it is now possible to engineer IgGs with altered affinities for FcRn, and t his has relevance to the modulation of Ige serum half-lift and maternofetal IgG transport for therapeutic applications.