Diversity in the CDR3 Region of VH Is Sufficient for Most Antibody Specificities

Xu, John L; Davis, Mark M

doi:10.1016/s1074-7613(00)00006-6

Cited by 779Monoclonal and Polyclonal Antibodies ResearchT-cell and B-cell Immunologyvaccines and immunoinformatics approaches

Diversity in the CDR3 Region of VH Is Sufficient for Most Antibody Specificities

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Xu, John L, Davis, Mark M·2000·Immunity

DOI 10.1016/s1074-7613(00)00006-6

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Abstract

All rearranging antigen receptor genes have one or two highly diverse complementarity determining regions (CDRs) among the six that typically form the ligand binding surface. We report here that, in the case of antibodies, diversity at one of these regions, CDR3 of the V(H) domain, is sufficient to permit otherwise identical IgM molecules to distinguish between a variety of hapten and protein antigens. Furthermore, we find that somatic mutation can allow such antibodies to achieve surprisingly high affinities. These results are consistent with a model in which the highly diverse CDR3 loops are the key determinant of specificity in antigen recognition in both T cell receptors (TCR) and antibodies, whereas the germline-encoded CDR1 and CDR2 sequences are much more cross-reactive.

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CDRH3 is very important for antigen recognition.
“CDRH3 possesses the highest sequence and structural diversity of the six CDRs [33] and is very important for antigen recognition [34, 35].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [35]

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“of the six CDRs [33] and is very important for antigen recognition [34, 35].”
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Authors: Xu, J. L., & Davis, M. M.
Affiliations: Stanford Medicine (US)
Howard Hughes Medical Institute (US)
Corresponding author: Davis, Mark M
ORCID: Davis, Mark M
Venue: Immunity
Publisher: Elsevier BV
Published: 2000-07
Volume: 13
Issue: 1
Pages: 37-45
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/s1074-7613(00)00006-6
OpenAlex: W2091477384
Cited by: 779
References: 81
Citations by year: 2026: 25 · 2025: 43 · 2024: 61 · 2023: 41 · 2022: 47 · 2021: 47 · 2020: 42 · 2019: 44 · 2018: 38 · 2017: 49 · 2016: 29 · 2015: 37 · 2014: 26 · 2013: 17 · 2012: 31
FWCI: 10.37
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4764 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords: CDR3 diversity, antibody specificity, somatic hypermutation, antigen recognition, hapten binding, IgM, T cell receptor diversity, antibody affinity
MeSH terms: Amino Acid Sequence, Animals, Antibody Affinity, Antibody Diversity, Antibody Specificity, Antigens, Dextrans, Haptens, Hemocyanins, Humans, Immunoglobulin G, Immunoglobulin M, Immunoglobulin Variable Region, Immunoglobulin Heavy Chains, Immunoglobulin kappa-Chains, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Ovalbumin, Polysaccharides, Bacterial, Sequence Analysis, Complementarity Determining Regions, Mice

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Diversity in the CDR3 Region of VH Is Sufficient for Most Antibody Specificities

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