The binding of soluble recombinant human Fcγ receptor I for human immunoglobulin G is conferred by its first and second extracellular domains

Asaoka, Yoshiharu; Hatayama, Kouta; Ide, T.; Tsumoto, K.; Tomita, Masahiro

doi:10.1016/j.molimm.2013.01.007

Cited by 12 publications

(21 citation statements)

References 26 publications

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“…Later, the second domain was also identified as playing a role in promoting high-affinity interactions between FcγRI and Fc 111 . Recent studies support the role of the second domain in increasing binding, and contest the importance of the third domain 107, 112 . Residues 171–176 of FcγRI form the FG-loop in FcγRI.…”

Section: Fc-fc Receptor Interactionsmentioning

confidence: 92%

A Perspective on the Structure and Receptor Binding Properties of Immunoglobulin G Fc

Hanson

Barb

2015

Biochemistry

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Recombinant antibodies spurred a revolution in medicine that saw the introduction of powerful therapeutics for treating a wide range of diseases, from cancers to autoimmune disorders and transplant rejection with more applications looming on the horizon. Many of these therapeutic monoclonal antibodies (mAbs) are based on human immunoglobulin G1 (IgG1), or at least contain a portion of the molecule. Most mAbs require interactions with cell surface receptors for efficacy, including the Fc γ receptors (FcγRs). High-resolution structural models of antibodies and antibody fragments have been available for nearly forty years, however, a thorough description of the structural features that determine the affinity with which antibodies interact with human receptors is not known. In this review we will cover the relevant history of IgG-related literature and how recent developments have changed our view of critical antibody-cell interactions at the atomic level with a nod to outstanding questions in the field and future prospects.

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Section: Fc-fc Receptor Interactionsmentioning

confidence: 92%

A Perspective on the Structure and Receptor Binding Properties of Immunoglobulin G Fc

Hanson

Barb

2015

Biochemistry

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“…The unique third domain has no contact role in the interaction of the receptor with human IgG1 and has been proposed as a ‘spacer’ to ‘separate’ the IgG interactive surface of the second domain from the cell membrane. SPR analysis using recombinant protein containing two or three ectodomains is consistent with this view . However, the proposition that the third domain acts only as a spacer is not supported by experiments where receptor variants lacking the third domain were expressed in a more physiological context on the cell surface.…”

Section: Structural and Functional Analysis Of The Interaction Of Hummentioning

confidence: 94%

“…Despite the perception of constant receptor occupancy, it is clear from experimental data that IgG dissociates readily from FccRI (11,12,17,18). Thus, it is plausible that FccRI is normally exchanging bound monomeric antibody with plasma or extravascular IgG and because of its higher affinity compared to the low-affinity receptors, it is more likely that small ICs or sparsely opsonized large complexes may be captured (19)(20)(21).…”

Section: Consequences Of Receptor Occupancymentioning

confidence: 99%

The high‐affinity receptor for IgG, FcγRI, of humans and non‐human primates

Chenoweth

Trist

Tan

et al. 2015

Immunological Reviews

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Non-human primate (NHP) models, especially involving macaques, are considered important models of human immunity and have been essential in preclinical testing for vaccines and therapeutics. Despite this, much less characterization of macaque Fc receptors has occurred compared to humans or mice. Much of the characterization of macaque Fc receptors so far has focused on the low-affinity Fc receptors, particularly FcγRIIIa. From these studies, it is clear that there are distinct differences between the human and macaque low-affinity receptors and their interaction with human IgG. Relatively little work has been performed on the high-affinity IgG receptor, FcγRI, especially in NHPs. This review will focus on what is currently known of how FcγRI interacts with IgG, from mutation studies and recent crystallographic studies of human FcγRI, and how amino acid sequence differences in the macaque FcγRI may affect this interaction. Additionally, this review will look at the functional consequences of differences in the amino acid sequences between humans and macaques.

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“…Indeed as a consequence of molecular engineering, and advanced in silico approaches it is possible to engineer a monoclonal antibody with high Fc binding affinity for the low-affinity variants of the FcγRIIIa (CD16) receptor (F 158 ) and the FcγRIIa (CD32) low-responder (H 131 ) on immune effector cells. Previous studies described the expression of recombinant soluble human FcγRs in E. coli, insects and mammalian cells [20][21][22]. However, to the best of our knowledge, expression of the extracellular domains of human using yeast expression system has not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2016

International Advanced Research Journal in Science, Engineering

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Genetic engineering technologies allow mass production of proteins for a variety of applications mainly in the biopharmaceutical industry. FcγRIIa (CD32a) and FcγRIIIa (CD16a) are antibodies cell surface receptors that mediate important immune functions. Fcγ receptors are currently the focus in developing novel therapeutic antibodies. Herein, we report the production at a high yields of genetically engineered soluble forms of the extracellular domain of the main genetic variants of CD16a (158F/V) (1.5mg/ml, 0.75mg/ml) and CD32a (131H/R) (5.8mg/ml, 0.9mg/ml) by the yeast Pichia pastoris. The Proteins were produced following induction using 1% methanol. SDS-PAGE and Western blot analysis of the protein purified on Ni+ column showed bands of ~45 kDa and ~25 kDa corresponding to CD16a and CD32a respectively. The production at a high yield of good quality recombinant Fcγ receptors in yeast is an important outcome because of their importance in the development of third generation therapeutic antibodies.

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The binding of soluble recombinant human Fcγ receptor I for human immunoglobulin G is conferred by its first and second extracellular domains

Cited by 12 publications

References 26 publications

A Perspective on the Structure and Receptor Binding Properties of Immunoglobulin G Fc

A Perspective on the Structure and Receptor Binding Properties of Immunoglobulin G Fc

The high‐affinity receptor for IgG, FcγRI, of humans and non‐human primates

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