Naturally occurring antibodies devoid of light chains
Abstract
Random association of VL and VH repertoires contributes considerably to antibody diversity. The diversity and the affinity are then increased by hypermutation in B cells located in germinal centres. Except in the case of 'heavy chain' disease, naturally occurring heavy-chain antibodies have not been described, although antigen binding has been demonstrated for separated heavy chains or cloned VH domains. Here we investigate the presence of considerable amounts of IgG-like material of M(r) 100K in the serum of the camel (Camelus dromedarius). These molecules are composed of heavy-chain dimers and are devoid of light chains, but nevertheless have an extensive antigen-binding repertoire, a finding that calls into question the role of light chains in the camel. Camel heavy-chain IgGs lack CH1, which in one IgG class might be structurally replaced by an extended hinge. Heavy-chain IgGs are a feature of all camelids. These findings open new perspectives in the engineering of antibodies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
VNAs offer some advantages over classical antibodies such as ease to engineer, improved heat and pH stability, and better tissue penetration.
“In general, VNAs offer some advantages over classical antibodies such as ease to engineer, improved heat and pH stability, and better tissue penetration (Hamers‐Casterman et al, 1993; van der Linden et al, 1999; Tillib et al, 2013).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Hamers‐Casterman et al, 1993
Cites
Hendershot, L., Bole, D., Köhler, G., & Kearney, J. F. (1987) · The Journal of cell biology · doi:10.1083/jcb.104.3.761 · Cited by 340 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Electrochemical Biosensors - Sensor Principles and Architectures
Grieshaber, D., MacKenzie, R., Vörös, J., & Reimhult, E. (2008) · Sensors · doi:10.3390/s80314000 · Cited by 2,329 · see citing works
Nanobodies: natural single-domain antibodies
Muyldermans, S. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-063011-092449 · Cited by 2,304 · see citing works
Self-citationTherapeutic antibodies: successes, limitations and hopes for the future
Chames, P., Van Regenmortel, M., Weiss, E., & Baty, D. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00190.x · Cited by 1,382 · see citing works
Targeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016 · see citing works
Properties, production, and applications of camelid single-domain antibody fragments
Harmsen, M. M., & De Haard, H. J. (2007) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-007-1142-2 · Cited by 809 · see citing works
“Sequence analysis (Hamers-Casterman et al. 1993; Muyldermans et al. 1994; Vu et al. 1997; Harmsen et al. 2000) and elucidation of the crystal structure (Desmyter et al.”
BackgroundInfluentialNanobodies and nanobody-based human heavy chain antibodies as antitumor therapeutics
Bannas, P., Hambach, J., & Koch-Nolte, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01603 · Cited by 572 · see citing works
van der Linden, R. H. J., Frenken, L. G. J., de Geus, B., Harmsen, M. M., Ruuls, R. C., Stok, W., de Ron, L., Wilson, S., Davis, P., & Verrips, C. T. (1999) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(99)00030-8 · Cited by 471 · see citing works
CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels
Chini, C. C. S., Peclat, T. R., Warner, G. M., Kashyap, S., Espindola-Netto, J. M., de Oliveira, G. C., Gomez, L. S., Hogan, K. A., Tarragó, M. G., Puranik, A. S., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00298-z · Cited by 349 · see citing works
Bispecific antibodies for cancer therapy: The light at the end of the tunnel?
Chames, P., & Baty, D. (2009) · mAbs · doi:10.4161/mabs.1.6.10015 · Cited by 336 · see citing works
Nanobody stabilization of G protein-coupled receptor conformational states
Steyaert, J., & Kobilka, B. K. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.06.011 · Cited by 234 · see citing works
Koide, A., Wojcik, J., Gilbreth, R. N., Hoey, R. J., & Koide, S. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.12.019 · Cited by 227 · see citing works
Structural basis of epitope recognition by heavy-chain camelid antibodies
Zavrtanik, U., Lukan, J., Loris, R., Lah, J., & Hadži, S. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.09.002 · Cited by 169 · see citing works
mRNA mediates passive vaccination against infectious agents, toxins, and tumors
Thran, M., Mukherjee, J., Pönisch, M., Fiedler, K., Thess, A., Mui, B. L., Hope, M. J., Tam, Y. K., Horscroft, N., Heidenreich, R., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707678 · Cited by 166 · see citing works
“In general, VNAs offer some advantages over classical antibodies such as ease to engineer, improved heat and pH stability, and better tissue penetration (Hamers-Casterman et al, 1993; van der Linden et al, 1999; Tillib et al, 2013).”
BackgroundAnalysis of nanobody paratopes reveals greater diversity than classical antibodies
Mitchell, L. S., & Colwell, L. J. (2018) · Protein Engineering Design and Selection · doi:10.1093/protein/gzy017 · Cited by 138 · see citing works
Radiolabeled nanobodies as theranostic tools in targeted radionuclide therapy of cancer
D’Huyvetter, M., Xavier, C., Caveliers, V., Lahoutte, T., Muyldermans, S., & Devoogdt, N. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.941803 · Cited by 124 · see citing works
Self-citationRecent agents targeting HIF‐1α for cancer therapy
Hu, Y., Liu, J., & Huang, H. (2013) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24390 · Cited by 113 · see citing works
Pantazes, R. J., & Maranas, C. D. (2010) · Protein Engineering Design and Selection · doi:10.1093/protein/gzq061 · Cited by 97 · see citing works
Analysis and modeling of the variable region of camelid single-domain antibodies
Sircar, A., Sanni, K. A., Shi, J., & Gray, J. J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100116 · Cited by 92 · see citing works
The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins
Feige, M. J., Gräwert, M. A., Marcinowski, M., Hennig, J., Behnke, J., Ausländer, D., Herold, E. M., Peschek, J., Castro, C. D., Flajnik, M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321502111 · Cited by 91 · see citing works
Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis
Arias, J. L., Unciti-Broceta, J. D., Maceira, J., del Castillo, T., Hernández-Quero, J., Magez, S., Soriano, M., & García-Salcedo, J. A. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.11.002 · Cited by 88 · see citing works
sdAb-DB: the single domain antibody database
Wilton, E. E., Opyr, M. P., Kailasam, S., Kothe, R. F., & Wieden, H.-J. (2018) · ACS Synthetic Biology · doi:10.1021/acssynbio.8b00407 · Cited by 84 · see citing works
Griffiths, K., Dolezal, O., Parisi, K., Angerosa, J., Dogovski, C., Barraclough, M., Sanalla, A., Casey, J., González, I., Perugini, M., et al. (2013) · Antibodies · doi:10.3390/antib2010066 · Cited by 64 · see citing works
Formatted single-domain antibodies can protect mice against infection with influenza virus (H5N2)
Tillib, S. V., Ivanova, T. I., Vasilev, L. A., Rutovskaya, M. V., Saakyan, S. A., Gribova, I. Y., Tutykhina, I. L., Sedova, E. S., Lysenko, A. A., Shmarov, M. M., et al. (2013) · Antiviral Research · doi:10.1016/j.antiviral.2012.12.014 · Cited by 54 · see citing works
VHH Antibodies: Reagents for Mycotoxin Detection in Food Products
Wang, J., Mukhtar, H., Ma, L., Pang, Q., & Wang, X. (2018) · Sensors · doi:10.3390/s18020485 · Cited by 53 · see citing works
Mikkilineni, L., Natrakul, D. A., Lam, N., Manasanch, E. E., Mann, J., Weissler, K. A., Wong, N., Brudno, J. N., Goff, S. L., Yang, J. C., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2023.12.018 · Cited by 16 · see citing works
Santana, H. M., Farias, B. J. C., Silva, M. D. S., da Silva, C. P., Eulálio, M. D. M. C., Ferreira e Ferreira, A. A., dos Reis, V. P., Ikenohuchi, Y. J., Paloschi, M. V., de Lima, A. M., et al. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116220 · Cited by 2 · see citing works
Campos Farias, B. J., Makoto Kayano, A., Barros Luiz, M., Maciel DE Lima, A., Suelen da Silva Morais, M., Moreira Mendes, L., Mota Santana, H., Reis Prado, N. D., Andrade Roberto, S., Martins Soares, A., et al. (2024) · Toxicon · doi:10.1016/j.toxicon.2024.107837 · Cited by 1 · see citing works
- Authors
- Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hammers, C., Songa, E. B., Bendahman, N., & Hammers, R.
- Affiliations
- Vrije Universiteit Brussel (BE)
- Venue
- Nature
- Published
- 1993-06
- Volume
- 363
- Issue
- 6428
- Pages
- 446-448
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2095553811
- Cited by
- 3,241
- References
- 1
- Citations by year
- 2026: 180 · 2025: 214 · 2024: 236 · 2023: 223 · 2022: 205 · 2021: 227 · 2020: 197 · 2019: 173 · 2018: 134 · 2017: 149 · 2016: 129 · 2015: 107 · 2014: 144 · 2013: 109 · 2012: 107
- FWCI
- 13.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Animal Diversity and Health Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- heavy-chain antibodies, camelids, Camelus dromedarius, antibody diversity, CH1 domain, antibody engineering
- MeSH terms
- Amino Acid Sequence, Animals, Antigens, Protozoan, Base Sequence, Camelus, DNA, Single-Stranded, Humans, Immunoglobulin G, Immunoglobulin Constant Regions, Immunoglobulin Variable Region, Immunoglobulin Heavy Chains, Molecular Sequence Data, Protein Conformation, Trypanosomiasis, Sequence Homology, Amino Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
