|
|
||||||||
The Journal of Immunology, Vol 147, Issue 5 1709-1719, Copyright © 1991 by American Association of Immunologists
ARTICLES |
EA Kabat and TT Wu
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
By examining a large database of amino acid sequences of antibodies of various specificities, we have found that many antibodies of distinctly different specificities assemble identical VL domains with different VH domains. In contrast, rarely is the same VH domain found in sets of antibodies of different specificities. We identified additional sets of antibodies of different specificities and identical sequences covering amino acid residues VH 1 to 94 and VL 1 to 95. In addition, there were segments of additional antibodies for which complete sequences were not available, but identities were seen in VL CDR1, VL CDR2, and VL CDR3 up to the VL-JL junction. The finding that there are many identical VL 1 to 95 segments with different VH 1 to 94 sequences, and vice versa, raises important questions as to the role of VH in influencing the conformation of VL and, conversely, the role of VL in influencing the conformation of VH. Evidence is also cited indicating that a single amino acid change may seriously disrupt site structure and in some instances abolish binding. Our findings suggest that it will be important in the future to investigate further conformational effects on antibody structure by using X-ray crystallography, nuclear magnetic resonance spectroscopy, or other methods, to obtain a better understanding of the functions and topography of antibody-combining sites.
This article has been cited by other articles:
![]() |
K. Yoshinaga, M. Matsumoto, M. Torikai, K. Sugyo, S. Kuroki, K. Nogami, R. Matsumoto, S. Hashiguchi, Y. Ito, T. Nakashima, et al. Ig L-chain Shuffling for Affinity Maturation of Phage Library-derived Human Anti-human MCP-1 Antibody Blocking its Chemotactic Activity J. Biochem., May 1, 2008; 143(5): 593 - 601. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Yoshihara, S. Takiguchi, A. Kyuno, K. Tanaka, S. Kuba, S. Hashiguchi, Y. Ito, T. Hashimoto, T. Iwatsubo, S. Tsuyama, et al. Immunoreactivity of Phage Library-derived Human Single-Chain Antibodies to Amyloid Beta Conformers In Vitro J. Biochem., April 1, 2008; 143(4): 475 - 486. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. C. Peterson, M. Gunnell, Y. Che, R. L. Goforth, F. I. Carroll, R. Henry, H. Liu, and S. M. Owens Using Hapten Design to Discover Therapeutic Monoclonal Antibodies for Treating Methamphetamine Abuse J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 30 - 39. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Qian, L. A. Diaz, J. Ye, and S. H. Clarke Dissecting the Anti-Desmoglein Autoreactive B Cell Repertoire in Pemphigus Vulgaris Patients J. Immunol., May 1, 2007; 178(9): 5982 - 5990. [Abstract] [Full Text] [PDF] |
||||
![]() |
E.-M. Krinner, J. Hepp, P. Hoffmann, S. Bruckmaier, L. Petersen, S. Petsch, L. Parr, I. Schuster, S. Mangold, G. Lorenczewski, et al. A highly stable polyethylene glycol-conjugated human single-chain antibody neutralizing granulocyte-macrophage colony stimulating factor at low nanomolar concentration Protein Eng. Des. Sel., October 1, 2006; 19(10): 461 - 470. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Yao, W. Chen, H. Luo, Q. Jiang, Z. Xia, L. Zang, J. Zuo, X. Wei, Z. Chen, X. Shen, et al. Identification of core functional region of murine IL-4 using peptide phage display and molecular modeling Int. Immunol., January 1, 2006; 18(1): 19 - 29. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. B. Koralov, T. I. Novobrantseva, K. Hochedlinger, R. Jaenisch, and K. Rajewsky Direct in vivo VH to JH rearrangement violating the 12/23 rule J. Exp. Med., February 7, 2005; 201(3): 341 - 348. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Dong, G. Stewart-Jones, N. Chen, P. Easterbrook, X. Xu, L. Papagno, V. Appay, M. Weekes, C. Conlon, C. Spina, et al. HIV-specific Cytotoxic T Cells from Long-Term Survivors Select a Unique T Cell Receptor J. Exp. Med., December 20, 2004; 200(12): 1547 - 1557. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. P. Weekes, M. R. Wills, J. G. P. Sissons, and A. J. Carmichael Long-Term Stable Expanded Human CD4+ T Cell Clones Specific for Human Cytomegalovirus Are Distributed in Both CD45RAhigh and CD45ROhigh Populations J. Immunol., November 1, 2004; 173(9): 5843 - 5851. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hashiguchi, T. Nakashima, A. Nitani, T. Yoshihara, K. Yoshinaga, Y. Ito, Y. Maeda, and K. Sugimura Human Fc{varepsilon}RI{alpha}-Specific Human Single-Chain Fv (scFv) Antibody with Antagonistic Activity toward IgE/Fc{varepsilon}RI{alpha}-Binding J. Biochem., January 1, 2003; 133(1): 43 - 49. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Bauer, M. Zemlin, M. Hummel, S. Pfeiffer, J. Karstaedt, G. Steinhauser, X. Xiao, H. Versmold, and C. Berek Diversification of Ig Heavy Chain Genes in Human Preterm Neonates Prematurely Exposed to Environmental Antigens J. Immunol., August 1, 2002; 169(3): 1349 - 1356. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. W. Schroeder Jr, L. Zhang, and J. B. Philips III Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life Blood, November 1, 2001; 98(9): 2745 - 2751. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nakouzi, P. Valadon, J. Nosanchuk, N. Green, and A. Casadevall Molecular Basis for Immunoglobulin M Specificity to Epitopes in Cryptococcus neoformans Polysaccharide That Elicit Protective and Nonprotective Antibodies Infect. Immun., May 1, 2001; 69(5): 3398 - 3409. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Monestier, P. Decker, J.-P. Briand, J. L. Gabriel, and S. Muller Molecular and Structural Properties of Three Autoimmune IgG Monoclonal Antibodies to Histone H2B J. Biol. Chem., April 28, 2000; 275(18): 13558 - 13563. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Johnson and T. T. Wu Kabat Database and its applications: 30 years after the first variability plot Nucleic Acids Res., January 1, 2000; 28(1): 214 - 218. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. P. Weekes, A. J. Carmichael, M. R. Wills, K. Mynard, and J. G. P. Sissons Human CD28-CD8+ T Cells Contain Greatly Expanded Functional Virus-Specific Memory CTL Clones J. Immunol., June 15, 1999; 162(12): 7569 - 7577. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Shiokawa, F. Mortari, J. O. Lima, C. Nunez, F. E. Bertrand III, P. M. Kirkham, S. Zhu, A. P. Dasanayake, and H. W. Schroeder Jr. IgM Heavy Chain Complementarity-Determining Region 3 Diversity Is Constrained by Genetic and Somatic Mechanisms Until Two Months After Birth J. Immunol., May 15, 1999; 162(10): 6060 - 6070. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. F. Lake, M. L. Salgaller, P. van der Bruggen, R. M. Bernstein, and J. J. Marchalonis Construction and binding analysis of recombinant single-chain TCR derived from tumor-infiltrating lymphocytes and a cytotoxic T lymphocyte clone directed against MAGE-1 Int. Immunol., May 1, 1999; 11(5): 745 - 751. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. P. Weekes, M. R. Wills, K. Mynard, A. J. Carmichael, and J. G. P. Sissons The Memory Cytotoxic T-Lymphocyte (CTL) Response to Human Cytomegalovirus Infection Contains Individual Peptide-Specific CTL Clones That Have Undergone Extensive Expansion In Vivo J. Virol., March 1, 1999; 73(3): 2099 - 2108. [Abstract] [Full Text] |
||||
![]() |
H. Jacobs, Y. Fukita, G. T.J. van der Horst, J. de Boer, G. Weeda, J. Essers, N. de Wind, B. P. Engelward, L. Samson, S. Verbeek, et al. Hypermutation of Immunoglobulin Genes in Memory B Cells of DNA Repair-deficient Mice J. Exp. Med., June 1, 1998; 187(11): 1735 - 1743. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. G. Nickerson, M.-H. Tao, H.-T. Chen, J. Larrick, and E. A. Kabat Human and Mouse Monoclonal Antibodies to Blood Group A Substance, Which Are Nearly Identical Immunochemically, Use Radically Different Primary Sequences J. Biol. Chem., May 26, 1995; 270(21): 12457 - 12465. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Haynes, E. Stura, D Hilvert, and I. Wilson Routes to catalysis: structure of a catalytic antibody and comparison with its natural counterpart Science, February 4, 1994; 263(5147): 646 - 652. [Abstract] [PDF] |
||||
![]() |
A. Desmyter, K. Decanniere, S. Muyldermans, and L. Wyns Antigen Specificity and High Affinity Binding Provided by One Single Loop of a Camel Single-domain Antibody J. Biol. Chem., July 6, 2001; 276(28): 26285 - 26290. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. T. Boder, K. S. Midelfort, and K. D. Wittrup Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity PNAS, September 26, 2000; 97(20): 10701 - 10705. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |