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The Rate of Dissociation Between Antibody and Antigen Determines the Efficiency of Antibody-Mediated Antigen Presentation to T Cells

Abstract : We analyzed the role of Ab affinity on Ab-mediated Ag uptake and presentation to T cells. Hen egg white lysozyme (HEL) was captured by bifunctional hybrid proteins (Fv-MalE) in which the variable fragment (Fv) of the anti-HEL mAb D1.3 was covalently linked to the Escherichia coli MalE protein. These complexes were targeted via two anti-MalE mAbs to an APC expressing a receptor for the Ab constant region. The combination of Fv-MalE and anti-MalE mAbs increased, specifically, HEL presentation. With this experimental system, we evaluated the impact of six different mutations, affecting the Fv-MalE complementarity determining regions, on the increase of HEL presentation by the corresponding hybrids. These mutations increase the dissociation rate constant (koff), and, thus, the dissociation constant of the HEL/Fv-MalE interaction, up to 650-fold, as compared with the wt Fv-MalE. Increasing the koff from 7 × 10−4 s−1 up to 300 × 10−4 s−1 did not interfere with the enhancement of HEL presentation. A mutant with a koff of 600 × 10−4 s−1 had a reduced enhancement ability, and mutants with koff higher than 5700 × 10−4 s−1 did not enhance HEL presentation at all. These results show that affinity determines the efficiency of Ab-mediated Ag presentation to T cells. One consequence is that affinity maturation in specific B lymphocytes can drastically enhance their ability to collaborate with T cells in an MHC-restricted way. This may contribute to the selection of high affinity B cell clones.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03525673
Contributor : Patrick England Connect in order to contact the contributor
Submitted on : Friday, January 14, 2022 - 6:44:28 AM
Last modification on : Thursday, April 7, 2022 - 10:10:29 AM

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  • HAL Id : pasteur-03525673, version 1
  • PUBMED : 9794380
  • WOS : 000076581100015

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Pierre Guermonprez, Patrick England, Hugues Bedouelle, Claude Leclerc. The Rate of Dissociation Between Antibody and Antigen Determines the Efficiency of Antibody-Mediated Antigen Presentation to T Cells. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 1998, 161 (9), pp.4542-8. ⟨pasteur-03525673⟩

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