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Single domain antibodies: promising experimental and therapeutic tools in infection and immunity.

Wesolowski J, Alzogaray V, Reyelt J, Unger M, Juarez K, Urrutia M, Cauerhff A, Danquah W, Rissiek B, Scheuplein F, Schwarz N, Adriouch S, Boyer O, Seman M, Licea A, Serreze DV, Goldbaum FA, Haag F, Koch-Nolte F - Med. Microbiol. Immunol. (2009)

Bottom Line: VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies.Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo.Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
Antibodies are important tools for experimental research and medical applications. Most antibodies are composed of two heavy and two light chains. Both chains contribute to the antigen-binding site which is usually flat or concave. In addition to these conventional antibodies, llamas, other camelids, and sharks also produce antibodies composed only of heavy chains. The antigen-binding site of these unusual heavy chain antibodies (hcAbs) is formed only by a single domain, designated VHH in camelid hcAbs and VNAR in shark hcAbs. VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies. The CDR3 region of these sdAbs possesses the extraordinary capacity to form long fingerlike extensions that can extend into cavities on antigens, e.g., the active site crevice of enzymes. Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo. Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes.

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Related in: MedlinePlus

Schematic diagram of the VHH domain of a camelid heavy chain antibody. a The three complementarity determining regions (CDRs) of the antigen-binding paratope are depicted as colored loops: CDR1 red, CDR2 green, and CDR3 blue. b The canonical disulfide bond connecting framework regions 1 and 3 (FR1 and FR3) in the two β-sheets of the immunoglobulin domain is indicated in yellow. Many camelid antibodies contain an additional disulfide bond (S–S) connecting the CDR3 with the end of the CDR1 (camels) or the beginning of the CDR2 (llamas). h Hinge, M transmembrane domain of membrane isoform, G glycosylation site, S stop codon of secretory isoform
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Fig2: Schematic diagram of the VHH domain of a camelid heavy chain antibody. a The three complementarity determining regions (CDRs) of the antigen-binding paratope are depicted as colored loops: CDR1 red, CDR2 green, and CDR3 blue. b The canonical disulfide bond connecting framework regions 1 and 3 (FR1 and FR3) in the two β-sheets of the immunoglobulin domain is indicated in yellow. Many camelid antibodies contain an additional disulfide bond (S–S) connecting the CDR3 with the end of the CDR1 (camels) or the beginning of the CDR2 (llamas). h Hinge, M transmembrane domain of membrane isoform, G glycosylation site, S stop codon of secretory isoform

Mentions: Most antibodies are composed of two heavy and two light chains (Fig. 1). Both chains contribute to the two identical antigen-binding sites, which are usually flat or concave. In addition to these conventional antibodies, camelids and sharks also produce unusual antibodies composed only of heavy chains (Fig. 1) [2, 3]. These peculiar heavy chain antibodies (hcAbs) lack light chains (and, in the case of camelid antibodies, also the CH1-domain). Therefore, the antigen-binding site of hcAbs is formed only by a single domain that is linked directly via a hinge region to the Fc-domain. The variable domain is designated VHH for camelid hcAbs (Fig. 2) and VNAR for shark hcAbs, and more generally, nanobody or single domain antibody (sdAb) [4].Fig. 1


Single domain antibodies: promising experimental and therapeutic tools in infection and immunity.

Wesolowski J, Alzogaray V, Reyelt J, Unger M, Juarez K, Urrutia M, Cauerhff A, Danquah W, Rissiek B, Scheuplein F, Schwarz N, Adriouch S, Boyer O, Seman M, Licea A, Serreze DV, Goldbaum FA, Haag F, Koch-Nolte F - Med. Microbiol. Immunol. (2009)

Schematic diagram of the VHH domain of a camelid heavy chain antibody. a The three complementarity determining regions (CDRs) of the antigen-binding paratope are depicted as colored loops: CDR1 red, CDR2 green, and CDR3 blue. b The canonical disulfide bond connecting framework regions 1 and 3 (FR1 and FR3) in the two β-sheets of the immunoglobulin domain is indicated in yellow. Many camelid antibodies contain an additional disulfide bond (S–S) connecting the CDR3 with the end of the CDR1 (camels) or the beginning of the CDR2 (llamas). h Hinge, M transmembrane domain of membrane isoform, G glycosylation site, S stop codon of secretory isoform
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2714450&req=5

Fig2: Schematic diagram of the VHH domain of a camelid heavy chain antibody. a The three complementarity determining regions (CDRs) of the antigen-binding paratope are depicted as colored loops: CDR1 red, CDR2 green, and CDR3 blue. b The canonical disulfide bond connecting framework regions 1 and 3 (FR1 and FR3) in the two β-sheets of the immunoglobulin domain is indicated in yellow. Many camelid antibodies contain an additional disulfide bond (S–S) connecting the CDR3 with the end of the CDR1 (camels) or the beginning of the CDR2 (llamas). h Hinge, M transmembrane domain of membrane isoform, G glycosylation site, S stop codon of secretory isoform
Mentions: Most antibodies are composed of two heavy and two light chains (Fig. 1). Both chains contribute to the two identical antigen-binding sites, which are usually flat or concave. In addition to these conventional antibodies, camelids and sharks also produce unusual antibodies composed only of heavy chains (Fig. 1) [2, 3]. These peculiar heavy chain antibodies (hcAbs) lack light chains (and, in the case of camelid antibodies, also the CH1-domain). Therefore, the antigen-binding site of hcAbs is formed only by a single domain that is linked directly via a hinge region to the Fc-domain. The variable domain is designated VHH for camelid hcAbs (Fig. 2) and VNAR for shark hcAbs, and more generally, nanobody or single domain antibody (sdAb) [4].Fig. 1

Bottom Line: VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies.Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo.Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
Antibodies are important tools for experimental research and medical applications. Most antibodies are composed of two heavy and two light chains. Both chains contribute to the antigen-binding site which is usually flat or concave. In addition to these conventional antibodies, llamas, other camelids, and sharks also produce antibodies composed only of heavy chains. The antigen-binding site of these unusual heavy chain antibodies (hcAbs) is formed only by a single domain, designated VHH in camelid hcAbs and VNAR in shark hcAbs. VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies. The CDR3 region of these sdAbs possesses the extraordinary capacity to form long fingerlike extensions that can extend into cavities on antigens, e.g., the active site crevice of enzymes. Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo. Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes.

Show MeSH
Related in: MedlinePlus