A heavy-chain antibody is an antibody which consists only of two heavy chains and lacks the two light chains usually found in antibodies.
In common antibodies, the antigen binding region consists of the variable domains of the heavy and light chains (VH and VL). Heavy-chain antibodies can bind antigens despite having only VH domains. This observation has led to the development of a new type of antibody fragments with potential use as drugs, so-called single-domain antibodies.[1]
In 1989 a group of biologists led by Raymond Hamers at the Free University Brussels investigated the immune system of dromedaries. In addition to the expected four-chain antibodies, they identified simpler antibodies consisting only of two heavy chains. This discovery was published in Nature in 1993.[2] In 1995 a research team at the University of Miami found a different type of heavy-chain antibodies in sharks.[3]
In cartilaginous fishesedit
A heavy-chain shark antibody (left) and a heavy-chain camelid antibody (middle) in comparison to a common antibody (right). Heavy chains are shown in a darker shade, light chains in a lighter shade.
The immunoglobulin new antigen receptor (IgNAR) of cartilaginous fishes (for example sharks) is a heavy-chain antibody. IgNAR shows significant structural differences to other antibodies. It has five constant domains (CH) per chain instead of the usual three, several disulfide bonds in unusual positions, and the complementarity-determining region 3 (CDR3) forms an extended loop covering the site which binds to a light chain in other antibodies. These differences, in combination with the phylogenetic age of the cartilaginous fishes, have led to the hypothesis that IgNAR could be more closely related to a primordial antigen-binding protein than the mammalian immunoglobulins. To test this hypothesis, it would be necessary to discover IgNAR or similar antibodies in vertebrates that are phylogenetically still older, like the jawless fishlamprey and hagfish.[4]Non-vertebrates do not have antibodies at all.
Sharks, and possibly other cartilaginous fishes, have immunoglobulin M (IgM) and immunoglobulin W (IgW) as well, both types with two heavy and two light chains.[5]
In camelidsedit
The only mammals with heavy-chain (IgG-like) antibodies are camelids such as dromedaries, camels, llamas and alpacas.[6] This is a secondary development: The heavy chains of these antibodies have lost one of their constant domains (CH1) and undergone modifications in the variable domain (VH), both structural elements necessary for the binding of light chains. In one subgroup, the missing CH1 seems to be replaced by an extended hinge region, as shown in the image.[1][2] Despite their different overall structure, camelid heavy-chain antibodies share several properties with IgNAR, for example the extended CDR3 loop and the conformation of the CDR1. It has been reasoned that these similarities are caused by functional requirements, or convergent evolution, rather than a genuine relationship.[4]
About 50% of the antibodies in camelids are of the ordinary mammalian heavy/light-chain type.[7] It is not known whether any type of animal has only heavy-chain antibodies and completely lacks the common type with two heavy and two light chains.
Heavy-chain camelid antibodies have been found to be just as specific as a regular antibody and in some cases they are more robust. As well, they are easily isolated using the same phage panning procedure used for traditional antibodies, allowing them to be cultured ex vivo in large concentrations.[citation needed] Phage-displayed dromedary camel VHH libraries have been made for isolating single-domain antibodies against SARS-CoV-2 and other virus infections.[citation needed] The smaller size and single domain make these antibodies easier to transform into bacterial cells for bulk production, making them ideal for research purposes.[8]
Referencesedit
^ abHarmsen, M. M.; Haard, H. J. (2007). "Properties, production, and applications of camelid single-domain antibody fragments". Applied Microbiology and Biotechnology. 77 (1): 13–22. doi:10.1007/s00253-007-1142-2. PMC2039825. PMID 17704915.
^Greenberg, A.S.; Avila, D.; Hughes, M.; Hughes, A.; McKinney, E.C.; Flajnik, M.F. (1995). "A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks". Nature. 374 (6518): 168–173. Bibcode:1995Natur.374..168G. doi:10.1038/374168a0. PMID 7877689. S2CID 4304231.
^ abStanfield, R.; Dooley, H.; Flajnik, M.; Wilson, I. (2004). "Crystal structure of a shark single-domain antibody V region in complex with lysozyme". Science. 305 (5691): 1770–1773. Bibcode:2004Sci...305.1770S. doi:10.1126/science.1101148. PMID 15319492. S2CID 25137728.
^Flajnik, M. F.; Dooley, H. (2009). The Generation and Selection of Single-Domain, V Region Libraries from Nurse Sharks. Methods in Molecular Biology. Vol. 562. pp. 71–82. doi:10.1007/978-1-60327-302-2_6. ISBN978-1-60327-301-5. PMID 19554288.
^Conrath, K. E.; Wernery, U.; Muyldermans, S.; Nguyen, V. K. (2003). "Emergence and evolution of functional heavy-chain antibodies in Camelidae". Developmental and Comparative Immunology. 27 (2): 87–103. doi:10.1016/S0145-305X(02)00071-X. PMID 12543123.
^Ghannam, A., Kumari, S., Muyldermans, S., & Abbady, A. Q. (2015). Camelid nanobodies with high affinity for broad bean mottle virus: a possible promising tool to immunomodulate plant resistance against viruses. Plant Molecular Biology, 1-15.
External linksedit
Wikilite: Biology of immunoglobulin light chains
January 01, 1970
heavy, chain, antibody, heavy, chain, antibody, antibody, which, consists, only, heavy, chains, lacks, light, chains, usually, found, antibodies, common, antibodies, antigen, binding, region, consists, variable, domains, heavy, light, chains, heavy, chain, ant. A heavy chain antibody is an antibody which consists only of two heavy chains and lacks the two light chains usually found in antibodies In common antibodies the antigen binding region consists of the variable domains of the heavy and light chains VH and VL Heavy chain antibodies can bind antigens despite having only VH domains This observation has led to the development of a new type of antibody fragments with potential use as drugs so called single domain antibodies 1 Contents 1 Discovery 2 In cartilaginous fishes 3 In camelids 4 References 5 External linksDiscovery editIn 1989 a group of biologists led by Raymond Hamers at the Free University Brussels investigated the immune system of dromedaries In addition to the expected four chain antibodies they identified simpler antibodies consisting only of two heavy chains This discovery was published in Nature in 1993 2 In 1995 a research team at the University of Miami found a different type of heavy chain antibodies in sharks 3 In cartilaginous fishes edit nbsp A heavy chain shark antibody left and a heavy chain camelid antibody middle in comparison to a common antibody right Heavy chains are shown in a darker shade light chains in a lighter shade The immunoglobulin new antigen receptor IgNAR of cartilaginous fishes for example sharks is a heavy chain antibody IgNAR shows significant structural differences to other antibodies It has five constant domains CH per chain instead of the usual three several disulfide bonds in unusual positions and the complementarity determining region 3 CDR3 forms an extended loop covering the site which binds to a light chain in other antibodies These differences in combination with the phylogenetic age of the cartilaginous fishes have led to the hypothesis that IgNAR could be more closely related to a primordial antigen binding protein than the mammalian immunoglobulins To test this hypothesis it would be necessary to discover IgNAR or similar antibodies in vertebrates that are phylogenetically still older like the jawless fish lamprey and hagfish 4 Non vertebrates do not have antibodies at all Sharks and possibly other cartilaginous fishes have immunoglobulin M IgM and immunoglobulin W IgW as well both types with two heavy and two light chains 5 In camelids editThe only mammals with heavy chain IgG like antibodies are camelids such as dromedaries camels llamas and alpacas 6 This is a secondary development The heavy chains of these antibodies have lost one of their constant domains CH1 and undergone modifications in the variable domain VH both structural elements necessary for the binding of light chains In one subgroup the missing CH1 seems to be replaced by an extended hinge region as shown in the image 1 2 Despite their different overall structure camelid heavy chain antibodies share several properties with IgNAR for example the extended CDR3 loop and the conformation of the CDR1 It has been reasoned that these similarities are caused by functional requirements or convergent evolution rather than a genuine relationship 4 About 50 of the antibodies in camelids are of the ordinary mammalian heavy light chain type 7 It is not known whether any type of animal has only heavy chain antibodies and completely lacks the common type with two heavy and two light chains Heavy chain camelid antibodies have been found to be just as specific as a regular antibody and in some cases they are more robust As well they are easily isolated using the same phage panning procedure used for traditional antibodies allowing them to be cultured ex vivo in large concentrations citation needed Phage displayed dromedary camel VHH libraries have been made for isolating single domain antibodies against SARS CoV 2 and other virus infections citation needed The smaller size and single domain make these antibodies easier to transform into bacterial cells for bulk production making them ideal for research purposes 8 References edit a b Harmsen M M Haard H J 2007 Properties production and applications of camelid single domain antibody fragments Applied Microbiology and Biotechnology 77 1 13 22 doi 10 1007 s00253 007 1142 2 PMC 2039825 PMID 17704915 a b Hamers Casterman C Atarhouch T Muyldermans S Robinson G Hamers C Songa EB Bendahman N Hamers R 3 June 1993 Naturally occurring antibodies devoid of light chains Nature 363 6428 446 8 Bibcode 1993Natur 363 446H doi 10 1038 363446a0 PMID 8502296 S2CID 4265902 Greenberg A S Avila D Hughes M Hughes A McKinney E C Flajnik M F 1995 A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks Nature 374 6518 168 173 Bibcode 1995Natur 374 168G doi 10 1038 374168a0 PMID 7877689 S2CID 4304231 a b Stanfield R Dooley H Flajnik M Wilson I 2004 Crystal structure of a shark single domain antibody V region in complex with lysozyme Science 305 5691 1770 1773 Bibcode 2004Sci 305 1770S doi 10 1126 science 1101148 PMID 15319492 S2CID 25137728 Flajnik M F Dooley H 2009 The Generation and Selection of Single Domain V Region Libraries from Nurse Sharks Methods in Molecular Biology Vol 562 pp 71 82 doi 10 1007 978 1 60327 302 2 6 ISBN 978 1 60327 301 5 PMID 19554288 Conrath K E Wernery U Muyldermans S Nguyen V K 2003 Emergence and evolution of functional heavy chain antibodies in Camelidae Developmental and Comparative Immunology 27 2 87 103 doi 10 1016 S0145 305X 02 00071 X PMID 12543123 Nanobodies Nanobody org 2006 Ghannam A Kumari S Muyldermans S amp Abbady A Q 2015 Camelid nanobodies with high affinity for broad bean mottle virus a possible promising tool to immunomodulate plant resistance against viruses Plant Molecular Biology 1 15 External links editWikilite Biology of immunoglobulin light chains Retrieved from https en wikipedia org w index php title Heavy chain antibody amp oldid 1187118439, wikipedia, wiki, book, books, library,
