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2009 ; 103
(ä): 77-115
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Chapter 4: Multitasking by exploitation of intracellular transport functions the
many faces of FcRn
#MMPMID19755184
Ward ES
; Ober RJ
Adv Immunol
2009[]; 103
(ä): 77-115
PMID19755184
show ga
The MHC Class I-related receptor, FcRn, transports antibodies of the
immunoglobulin G (IgG) class within and across a diverse array of different cell
types. Through this transport, FcRn serves multiple roles throughout adult life
that extend well beyond its earlier defined function of transcytosing IgGs from
mother to offspring. These roles include the maintenance of IgG levels and the
delivery of antigen in the form of immune complexes to degradative compartments
within cells. Recent studies have led to significant advances in knowledge of the
intracellular trafficking of FcRn and (engineered) IgGs at both the molecular and
cellular levels. The engineering of FcRn-IgG (or Fc) interactions to generate
antibodies of increased longevity represents an area of active interest,
particularly in the light of the expanding use of antibodies in therapy. The
strict pH dependence of FcRn-IgG interactions, with binding at pH 6 that becomes
essentially undetectable as near neutral pH is approached, is essential for
efficient transport. The requirement for retention of low affinity at near
neutral pH increases the complexity of engineering antibodies for increased
half-life. Conversely, engineered IgGs that have gained significant binding for
FcRn at this pH can be potent inhibitors of FcRn that lower endogenous IgG levels
and have multiple potential uses as therapeutics. In addition, molecular studies
of FcRn-IgG interactions indicate that mice have limitations as preclinical
models for FcRn function, primarily due to cross-species differences in
FcRn-binding specificity.
|Animals
[MESH]
|Histocompatibility Antigens Class I/*immunology
[MESH]