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Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG
Abstract
Cellular receptors for IgG (Fc gamma R) mediate important protective functions. By using site-specific mutants of a chimeric antibody (mouse V H domain and L chain; human IgG3 C H domains), we have demonstrated that human Fc gamma RI interacts with a site in the lower hinge of human IgG (residues 234 to 237) and that this interaction dictates Fc gamma RI-mediated superoxide generation. Mutations at position 235 resulted in the most profound reductions in Fc gamma RI recognition. We have also mapped an interaction site for Fc gamma RII to the same region; however, mutations at position 234 and 237 resulted in the greatest reductions in Fc gamma RII recognition. The two receptors appear to recognize overlapping but nonidentical sites on the lower hinge of IgG. Deviations from the optimal motif 234-Leu-Leu-Gly-Gly-237 may then explain the human IgG subclass specificity profile for human Fc gamma RI and Fc gamma RII.
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Citations
Cited by
IgG Subclasses and Allotypes: From Structure to Effector Functions
Vidarsson, G., Dekkers, G., & Rispens, T. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00520 · Cited by 2,667
Schlothauer, T., Herter, S., Koller, C. F., Grau-Richards, S., Steinhart, V., Spick, C., Kubbies, M., Klein, C., Umaña, P., & Mössner, E. (2016) · Protein Engineering Design and Selection · doi:10.1093/protein/gzw040 · Cited by 425
IgG Fc engineering to modulate antibody effector functions
Wang, X., Mathieu, M., & Brezski, R. J. (2018) · Protein & Cell · doi:10.1007/s13238-017-0473-8 · Cited by 356
Antibodies to combat viral infections: development strategies and progress
Pantaleo, G., Correia, B., Fenwick, C., Joo, V. S., & Perez, L. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00495-3 · Cited by 279
Isotype and glycoform selection for antibody therapeutics
Jefferis, R. (2012) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2012.03.021 · Cited by 252
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Metadata
- Authors
- Lund, J., Winter, G., Jones, P. T., Pound, J. D., Tanaka, T., Walker, M. R., Artymiuk, P. J., Arata, Y., Burton, D. R., Jefferis, R., & Woof, J. M.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1991-10
- Volume
- 147
- Issue
- 8
- Pages
- 2657-2662
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1502725684
- Cited by
- 212
- References
- 0
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG. https://app.cochat.ai/papers/10.4049/jimmunol.147.8.2657
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- Lund, J., Winter, G., Jones, P. T., Pound, J. D., Tanaka, T., Walker, M. R., Artymiuk, P. J., Arata, Y., Burton, D. R., Jefferis, R., & Woof, J. M. (1991). Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG. The Journal of Immunology. https://doi.org/10.4049/jimmunol.147.8.2657
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