The MHC Class I-Like IgG Receptor Controls Perinatal IgG Transport, IgG Homeostasis, and Fate of IgG-Fc-Coupled Drugs
Abs of the IgG isotype are efficiently transported from mother to neonate and have an extended serum t(1/2) compared with Abs of other isotypes. Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To under...
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| Veröffentlicht in: | The Journal of immunology (1950) 2003-04, Vol.170 (7), p.3528-3533 |
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| container_title | The Journal of immunology (1950) |
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| creator | Roopenian, Derry C Christianson, Gregory J Sproule, Thomas J Brown, Aaron C Akilesh, Shreeram Jung, Nadja Petkova, Stefka Avanessian, Lia Choi, Eun Young Shaffer, Daniel J Eden, Peter A Anderson, Clark L |
| description | Abs of the IgG isotype are efficiently transported from mother to neonate and have an extended serum t(1/2) compared with Abs of other isotypes. Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To understand the phenotypes imposed by FcRn, we produced and analyzed mice with a defective FcRn gene. The results provide direct evidence that perinatal IgG transport and protection of IgG from catabolism are mediated by FcRn, and that the latter function is key to IgG homeostasis, essential for generating a potent IgG response to foreign Ags, and the basis of enhanced efficacy of Fc-IgG-based therapeutics. FcRn is therefore a promising therapeutic target for enhancing protective humoral immunity, treating autoimmune disease, and improving drug efficacy. |
| doi_str_mv | 10.4049/jimmunol.170.7.3528 |
| format | Article |
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Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To understand the phenotypes imposed by FcRn, we produced and analyzed mice with a defective FcRn gene. The results provide direct evidence that perinatal IgG transport and protection of IgG from catabolism are mediated by FcRn, and that the latter function is key to IgG homeostasis, essential for generating a potent IgG response to foreign Ags, and the basis of enhanced efficacy of Fc-IgG-based therapeutics. 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Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To understand the phenotypes imposed by FcRn, we produced and analyzed mice with a defective FcRn gene. The results provide direct evidence that perinatal IgG transport and protection of IgG from catabolism are mediated by FcRn, and that the latter function is key to IgG homeostasis, essential for generating a potent IgG response to foreign Ags, and the basis of enhanced efficacy of Fc-IgG-based therapeutics. FcRn is therefore a promising therapeutic target for enhancing protective humoral immunity, treating autoimmune disease, and improving drug efficacy.</description><subject>Abatacept</subject><subject>Animals</subject><subject>Animals, Newborn - genetics</subject><subject>Animals, Newborn - growth & development</subject><subject>Animals, Newborn - immunology</subject><subject>CD40 Ligand - immunology</subject><subject>Crosses, Genetic</subject><subject>Female</subject><subject>Half-Life</subject><subject>Histocompatibility Antigens Class I - physiology</subject><subject>Homeostasis - immunology</subject><subject>Humans</subject><subject>Immune Sera - administration & dosage</subject><subject>Immune Sera - metabolism</subject><subject>Immunity, Cellular - genetics</subject><subject>Immunoconjugates - administration & dosage</subject><subject>Immunoconjugates - metabolism</subject><subject>Immunoglobulin G - biosynthesis</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - metabolism</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - metabolism</subject><subject>Injections, Intraperitoneal</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Protein Transport - genetics</subject><subject>Protein Transport - immunology</subject><subject>Receptors, Fc - deficiency</subject><subject>Receptors, Fc - genetics</subject><subject>Receptors, Fc - metabolism</subject><subject>Receptors, IgG - physiology</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2P0zAQhi0EYsuyvwAJ-QSXTbEdf8RHFOi2UleLUPdsOcm4zeLEwU5U8e9Jt0Vw4zSaeZ95Lw9C7yhZcsL1p6e266Y--CVVZKmWuWDFC7SgQpBMSiJfogUhjGVUSXWF3qT0RAiRhPHX6IoyyaWkfIGm3QHw_brEpbcp4U22bX8A3uzv8HeoYRhDxGXoxxh8wt8gtr0drX_Od9H2aQhxvH1e16GDkEab2nSLbd_glR0BB3cKs1WdlWEaPDT4S5z26S165axPcHOZ1-hx9XVXrrPtw92m_LzNaq7EmFVWW1cxIbg4HaSzmrtC1UWueUWhkVpD1aimkDkDxomDRjhwNGeC1kS7_Bp9OPcOMfycII2ma1MN3tsewpSMyikRTJL_grSQOqeaz2B-BusYUorgzBDbzsZfhhJz0mL-aDGzFqPMScv89f5SP1UdNH9_Lh5m4OMZOLT7w7GNYFJnvZ9xao7H4z9VvwG5RZcy</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>Roopenian, Derry C</creator><creator>Christianson, Gregory J</creator><creator>Sproule, Thomas J</creator><creator>Brown, Aaron C</creator><creator>Akilesh, Shreeram</creator><creator>Jung, Nadja</creator><creator>Petkova, Stefka</creator><creator>Avanessian, Lia</creator><creator>Choi, Eun Young</creator><creator>Shaffer, Daniel J</creator><creator>Eden, Peter A</creator><creator>Anderson, Clark L</creator><general>Am Assoc Immnol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20030401</creationdate><title>The MHC Class I-Like IgG Receptor Controls Perinatal IgG Transport, IgG Homeostasis, and Fate of IgG-Fc-Coupled Drugs</title><author>Roopenian, Derry C ; Christianson, Gregory J ; Sproule, Thomas J ; Brown, Aaron C ; Akilesh, Shreeram ; Jung, Nadja ; Petkova, Stefka ; Avanessian, Lia ; Choi, Eun Young ; Shaffer, Daniel J ; Eden, Peter A ; Anderson, Clark L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-ba9afb25545c4756fa94f87c8394b1ed699ebd7d8632e240fed5fef13251c09f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Abatacept</topic><topic>Animals</topic><topic>Animals, Newborn - genetics</topic><topic>Animals, Newborn - growth & development</topic><topic>Animals, Newborn - immunology</topic><topic>CD40 Ligand - immunology</topic><topic>Crosses, Genetic</topic><topic>Female</topic><topic>Half-Life</topic><topic>Histocompatibility Antigens Class I - physiology</topic><topic>Homeostasis - immunology</topic><topic>Humans</topic><topic>Immune Sera - administration & dosage</topic><topic>Immune Sera - metabolism</topic><topic>Immunity, Cellular - genetics</topic><topic>Immunoconjugates - administration & dosage</topic><topic>Immunoconjugates - metabolism</topic><topic>Immunoglobulin G - biosynthesis</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin G - metabolism</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - metabolism</topic><topic>Injections, Intraperitoneal</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Protein Transport - genetics</topic><topic>Protein Transport - immunology</topic><topic>Receptors, Fc - deficiency</topic><topic>Receptors, Fc - genetics</topic><topic>Receptors, Fc - metabolism</topic><topic>Receptors, IgG - physiology</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roopenian, Derry C</creatorcontrib><creatorcontrib>Christianson, Gregory J</creatorcontrib><creatorcontrib>Sproule, Thomas J</creatorcontrib><creatorcontrib>Brown, Aaron C</creatorcontrib><creatorcontrib>Akilesh, Shreeram</creatorcontrib><creatorcontrib>Jung, Nadja</creatorcontrib><creatorcontrib>Petkova, Stefka</creatorcontrib><creatorcontrib>Avanessian, Lia</creatorcontrib><creatorcontrib>Choi, Eun Young</creatorcontrib><creatorcontrib>Shaffer, Daniel J</creatorcontrib><creatorcontrib>Eden, Peter A</creatorcontrib><creatorcontrib>Anderson, Clark L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roopenian, Derry C</au><au>Christianson, Gregory J</au><au>Sproule, Thomas J</au><au>Brown, Aaron C</au><au>Akilesh, Shreeram</au><au>Jung, Nadja</au><au>Petkova, Stefka</au><au>Avanessian, Lia</au><au>Choi, Eun Young</au><au>Shaffer, Daniel J</au><au>Eden, Peter A</au><au>Anderson, Clark L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The MHC Class I-Like IgG Receptor Controls Perinatal IgG Transport, IgG Homeostasis, and Fate of IgG-Fc-Coupled Drugs</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>170</volume><issue>7</issue><spage>3528</spage><epage>3533</epage><pages>3528-3533</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Abs of the IgG isotype are efficiently transported from mother to neonate and have an extended serum t(1/2) compared with Abs of other isotypes. Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To understand the phenotypes imposed by FcRn, we produced and analyzed mice with a defective FcRn gene. The results provide direct evidence that perinatal IgG transport and protection of IgG from catabolism are mediated by FcRn, and that the latter function is key to IgG homeostasis, essential for generating a potent IgG response to foreign Ags, and the basis of enhanced efficacy of Fc-IgG-based therapeutics. FcRn is therefore a promising therapeutic target for enhancing protective humoral immunity, treating autoimmune disease, and improving drug efficacy.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>12646614</pmid><doi>10.4049/jimmunol.170.7.3528</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of immunology (1950), 2003-04, Vol.170 (7), p.3528-3533 |
| issn | 0022-1767 1550-6606 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Abatacept Animals Animals, Newborn - genetics Animals, Newborn - growth & development Animals, Newborn - immunology CD40 Ligand - immunology Crosses, Genetic Female Half-Life Histocompatibility Antigens Class I - physiology Homeostasis - immunology Humans Immune Sera - administration & dosage Immune Sera - metabolism Immunity, Cellular - genetics Immunoconjugates - administration & dosage Immunoconjugates - metabolism Immunoglobulin G - biosynthesis Immunoglobulin G - blood Immunoglobulin G - metabolism Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - metabolism Injections, Intraperitoneal Male Mice Mice, Inbred C57BL Mice, Transgenic Protein Transport - genetics Protein Transport - immunology Receptors, Fc - deficiency Receptors, Fc - genetics Receptors, Fc - metabolism Receptors, IgG - physiology Transcription Factors - biosynthesis Transcription Factors - genetics |
| title | The MHC Class I-Like IgG Receptor Controls Perinatal IgG Transport, IgG Homeostasis, and Fate of IgG-Fc-Coupled Drugs |
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