Fragment crystallizable region
Thefragment crystallizable region(Fc region) is the tail region of anantibodythat interacts with cell surface receptors calledFc receptorsand some proteins of thecomplement system.This region allows antibodies to activate theimmune system,for example, through binding toFc receptors.InIgG,IgAandIgDantibodyisotypes,the Fc region is composed of two identical protein fragments, derived from the second and third constantdomainsof the antibody's twoheavy chains;IgMandIgEFc regions contain three heavy chain constant domains (CHdomains 2–4) in eachpolypeptidechain.[1][2]The Fc regions of IgGs bear a highly conserved N-glycosylation site.[3][4]Glycosylationof the Fc fragment is essential for Fc receptor-mediated activity.[5]TheN-glycansattached to this site are predominantly core-fucosylateddiantennary structures of the complex type. In addition, small amounts of these N-glycans also bear bisecting GlcNAc and α-2,6 linkedsialic acidresidues.[3]
The other part of an antibody, called theFab region,contains variable sections that define the specific target that the antibody can bind. By contrast, the Fc region of all antibodies in a class are the same for each species; they are constant rather than variable. The Fc region is, therefore, sometimes incorrectly termed the "fragment constant region".
Fc binds to various cellreceptorsandcomplementproteins. In this way, it mediates differentphysiologicaleffects of antibodies (detection ofopsonized particles;celllysis;degranulationofmast cells,basophils,andeosinophils;and other processes).[6]
Engineered Fc fragments
[edit]In a new development in the field of antibody-based therapeutics, the Fc region ofimmunoglobulinshas been engineered to contain anantigen-binding site.[7]This type ofantigen-binding fragmentis calledFcab.Fcab fragments can be inserted into a full immunoglobulin by swapping the Fc region, thus obtaining abispecific antibody(with both Fab and Fcab regions containing distinct binding sites). These bispecific monoclonal antibodies are sometimes referred to as mAb2.[8]
See also
[edit]References
[edit]- ^Janeway, CA Jr.;et al. (2001).Immunobiology(5th ed.). Garland Publishing.ISBN978-0-8153-3642-6.
- ^Larsson, Lars-Inge (September 1988).Immunocytochemistry: Theory and practice.Crc Press.ISBN978-0-8493-6078-7.
- ^abStadlmann J, Pabst M, Kolarich D, Kunert R, Altmann F (2008). "Analysis of immunoglobulin glycosylation by LC-ESI-MS of glycopeptides and oligosaccharides".Proteomics.8(14): 2858–2871.doi:10.1002/pmic.200700968.PMID18655055.S2CID22821543.
- ^Stadlmann J, Weber A, Pabst M, Anderle H, Kunert R, Ehrlich HJ, Peter Schwarz H, Altmann F (2009). "A close look at human IgG sialylation and subclass distribution after lectin fractionation".Proteomics.9(17): 4143–4153.doi:10.1002/pmic.200800931.PMID19688751.S2CID19147733.
- ^Peipp M, Lammerts van Bueren JJ, Schneider-Merck T, Bleeker WW, Dechant M, Beyer T, Repp R, van Berkel PH, Vink T, van de Winkel JG, Parren PW, Valerius T (2008)."Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells".Blood.112(6): 2390–2399.doi:10.1182/blood-2008-03-144600.PMID18566325.
- ^Paul, William (2013).Fundamental Immunology(Seventh ed.). Lippincott Williams & Wilkins. p. 1401–142.ISBN978-1-4511-1783-7.Retrieved31 December2015.
- ^Wozniak-Knopp G, Bartl S, Bauer A, Mostageer M, Woisetschläger M, Antes B, Ettl K, Kainer M, Weberhofer G, Wiederkum S, Himmler G, Mudde GC, Rüker F (2010)."Introducing antigen-binding sites in structural loops of immunoglobulin constant domains: Fc fragments with engineered HER2/neu-binding sites and antibody properties".Protein Eng Des.23(4): 289–297.doi:10.1093/protein/gzq005.PMID20150180.
- ^"MAb2™ Bispecific Monoclonal Antibodies".Archived fromthe originalon 2013-07-08.Retrieved2013-08-13.