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Titolo:
The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans
Autore:
Firan, M; Bawdon, R; Radu, C; Ober, RJ; Eaken, D; Antohe, F; Ghetie, V; Ward, ES;
Indirizzi:
Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Med Ctr, Ctr Immunol, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Dept Gynecol & Obstet, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 ept Gynecol & Obstet, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Ctr Canc Immunobiol, Dallas, TX 75390 USA Univ Texas, Dept Elect Engn, Richardson, TX 75083 USA Univ Texas Richardson TX USA 75083 t Elect Engn, Richardson, TX 75083 USA
Titolo Testata:
INTERNATIONAL IMMUNOLOGY
fascicolo: 8, volume: 13, anno: 2001,
pagine: 993 - 1002
SICI:
0953-8178(200108)13:8<993:TMCIRF>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFUSED HUMAN-PLACENTA; NATURAL-KILLER-CELLS; AMINO-ACID-RESIDUES; IMMUNOGLOBULIN-G; CRYSTAL-STRUCTURE; MURINE IGG1; NEONATAL RAT; COMPLEX; TRANSPORT; BINDING;
Keywords:
catabolism; human IgG; neonatal Fc receptor; placental transport;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Ward, ES Univ Texas, SW Med Ctr, Ctr Immunol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA Univ Texas 5323 Harry Hines Blvd Dallas TX USA 75390 TX 75390 USA
Citazione:
M. Firan et al., "The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans", INT IMMUNOL, 13(8), 2001, pp. 993-1002

Abstract

The transfer of maternal gamma -globulin (IgG) provides the neonate with humoral immunity during early life. In humans, maternal IgG is transported across the placenta during the third trimester of pregnancy. The expression of the MHC class I-related receptor, FcRn, in the human placenta suggests that this Fc receptor might be involved in the delivery of maternal IgG, butdirect evidence to support this is lacking. In the current study an ex vivo placental model has been used to analyze the maternofetal transfer of a recombinant, humanized (IgG1) antibody in which His435 has been mutated to alanine (H435A). In vitro binding studies using surface plasmon resonance indicate that the mutation ablates binding of the antibody to recombinant mouse and human FcRn. Relative to the wild-type antibody, the H435A mutant is deficient in transfer across the placenta. Significantly, the mutation doesnot affect binding to Fc gamma RIII, an FcR that has been suggested in earlier studies to mediate the transfer of maternal IgG. The analyses demonstrate that binding of an IgG to FcRn is a prerequisite for transport across the perfused placenta. FcRn therefore plays a central role in the maternofetal delivery of IgG and this has implications for the use of protein engineering to improve the properties of therapeutic antibodies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 23:49:18