IgG Fc domains that bind C1q but not effector Fc3 receptors delineate the importance of complement-mediated effector functions

Nature Immunology

Volumn 18, Issue 8, 2017, Pages 889-898

  Lee, Chang Han ^a   Romain, Gabrielle ^b   Yan, Wupeng ^c   Watanabe, Makiko ^a   Charab, Wissam ^a   Todorova, Biliana ^d,e   Lee, Jiwon ^a   Triplett, Kendra ^c   Donkor, Moses ^a,i   Lungu, Oana I ^a   Lux, Anja ^f   Marshall, Nicholas ^a,i,j   Lindorfer, Margaret A ^g   Goff, Odile Richard Le ^d,e   Balbino, Bianca ^d,e,h   Kang, Tae Hyun ^a   Tanno, Hidetaka ^a   Delidakis, George ^a   Alford, Corrine ^a   Taylor, Ronald P ^g   Nimmerjahn, Falk ^f   Varadarajan, Navin ^b   Bruhns, Pierre ^d,e   Zhang, Yan Jessie ^c   Georgiou, George ^a,c   more..

^a The University of Texas at Austin   (United States)

^b UNIVERSITY OF HOUSTON   (United States)

^c UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^d INSTITUT PASTEUR   (France)

^e INSERM   (France)

^f UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^g UNIVERSITY OF VIRGINIA   (United States)

^h SORBONNE UNIVERSITÉ   (France)

ⁱ MEDIMMUNE   (United States)

^j MERCK RESEARCH LABORATORIES   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT COMPONENT C1Q; IMMUNOGLOBULIN FC FRAGMENT; OFATUMUMAB; RITUXIMAB; FC RECEPTOR; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CELL FUNCTION; CELL KINETICS; COMPLEMENT ACTIVATION; COMPLEMENT DEPENDENT CYTOTOXICITY; CONTROLLED STUDY; EFFECTOR CELL; FEMALE; HUMAN; HUMAN CELL; IMMUNOGLOBULIN STRUCTURE; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PH; PHAGOCYTOSIS; POLYMORPHONUCLEAR CELL; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS; TARGET CELL; ANIMAL; BURKITT LYMPHOMA; CRYSTALLIZATION; CYTOTOXICITY; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOLOGY; IMMUNOTHERAPY; LIQUID CHROMATOGRAPHY; LYMPHOMA, B-CELL; LYMPHOMA, LARGE B-CELL, DIFFUSE; MASS SPECTROMETRY; METABOLISM; NEOPLASMS; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; SIZE EXCLUSION CHROMATOGRAPHY; SURFACE PLASMON RESONANCE; TANDEM MASS SPECTROMETRY; TUMOR CELL LINE; X RAY CRYSTALLOGRAPHY;

ANIMALS; ANTIBODIES, MONOCLONAL; BURKITT LYMPHOMA; CELL LINE, TUMOR; CHROMATOGRAPHY, GEL; CHROMATOGRAPHY, LIQUID; COMPLEMENT C1Q; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; CYTOTOXICITY, IMMUNOLOGIC; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; IMMUNOGLOBULIN FC FRAGMENTS; IMMUNOGLOBULIN G; IMMUNOTHERAPY; IN VITRO TECHNIQUES; LYMPHOMA, B-CELL; LYMPHOMA, LARGE B-CELL, DIFFUSE; MASS SPECTROMETRY; MICE; NEOPLASMS; PHAGOCYTOSIS; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; RECEPTORS, IGG; SURFACE PLASMON RESONANCE; TANDEM MASS SPECTROMETRY;

EID: 85025839005     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni.3770     Document Type: Article

References (63)

1. Weiner, G.J. Building better monoclonal antibody-based therapeutics. Nat. Rev. Cancer 15, 361-370 (2015).
2. Nimmerjahn, F. &Ravetch, J.V. Translating basic mechanisms of IgG effector activity into next generation cancer therapies. Cancer Immun. 12, 13 (2012).
3. Pincetic, A. et al. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat. Immunol. 15, 707-716 (2014).
4. Li, F.J. et al. Emerging roles for the FCRL family members in lymphocyte biology and disease. Curr. Top. Microbiol. Immunol. 382, 29-50 (2014).
5. van de Donk, N.W.C.J. et al. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol. Rev. 270, 95-112 (2016).
6. Ricklin, D., Hajishengallis, G., Yang, K. &Lambris, J.D. Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 11, 785-797 (2010).
7. Dunkelberger, J.R. &Song, W.-C. Complement and its role in innate and adaptive immune responses. Cell Res. 20, 34-50 (2010).
8. Hess, C. &Kemper, C. Complement-mediated regulation of metabolism and basic cellular processes. Immunity 45, 240-254 (2016).
9. Sondermann, P. &Szymkowski, D.E. Harnessing Fc receptor biology in the design of therapeutic antibodies. Curr. Opin. Immunol. 40, 78-87 (2016).
10. Bruhns, P. &Jönsson, F. Mouse and human FcR effector functions. Immunol. Rev. 268, 25-51 (2015).
11. Taylor, R.P. &Lindorfer, M.A. The role of complement in mAb-based therapies of cancer. Methods 65, 18-27 (2014).
12. Di Gaetano, N. et al. Complement activation determines the therapeutic activity of rituximab in vivo. J. Immunol. 171, 1581-1587 (2003).
13. Bruhns, P. et al. Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses. Blood 113, 3716-3725 (2009).
14. Lux, A., Yu, X., Scanlan, C.N. &Nimmerjahn, F. Impact of immune complex size and glycosylation on IgG binding to human FcγRs. J. Immunol. 190, 4315-4323 (2013).
15. Golay, J. &Introna, M. Mechanism of action of therapeutic monoclonal antibodies: promises and pitfalls of in vitro and in vivo assays. Arch. Biochem. Biophys. 526, 146-153 (2012).
16. Vafa, O. et al. An engineered Fc variant of an IgG eliminates all immune effector functions via structural perturbations. Methods 65, 114-126 (2014).
17. Arduin, E. et al. Highly reduced binding to high and low affinity mouse Fcγ receptors by L234A/L235A and N297A Fc mutations engineered into mouse IgG2a. Mol. Immunol. 63, 456-463 (2015).
18. Schreiber, A.D. &Frank, M.M. Role of antibody and complement in the immune clearance and destruction of erythrocytes. II. Molecular nature of IgG and IgM complement-fixing sites and effects of their interaction with serum. J. Clin. Invest. 51, 583-589 (1972).
19. Ackerman, M. &Nimmerjahn, F. Antibody Fc: Linking Adaptive and Innate Immunity (Academic Press, 2013).
20. Wang, S.-Y., Racila, E., Taylor, R.P. &Weiner, G.J. NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement. Blood 111, 1456-1463 (2008).
21. Harvey, B.R. et al. Anchored periplasmic expression, a versatile technology for the isolation of high-affinity antibodies from Escherichia coli-expressed libraries. Proc. Natl. Acad. Sci. USA 101, 9193-9198 (2004).
22. Jung, S.T. et al. Effective phagocytosis of low Her2 tumor cell lines with engineered, aglycosylated IgG displaying high FcγRIIa affinity and selectivity. ACS Chem. Biol. 8, 368-375 (2013).
23. Borrok, M.J., Jung, S.T., Kang, T.H., Monzingo, A.F. &Georgiou, G. Revisiting the role of glycosylation in the structure of human IgG Fc. ACS Chem. Biol. 7, 1596-1602 (2012).
24. Pawluczkowycz, A.W. et al. Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): considerably higher levels of CDC are induced by OFA than by RTX. J. Immunol. 183, 749-758 (2009).
25. Teeling, J.L. et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 104, 1793-1800 (2004).
26. Boross, P. &Leusen, J.H.W. Mechanisms of action of CD20 antibodies. Am. J. Cancer Res. 2, 676-690 (2012).
27. Teeling, J.L. et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J. Immunol. 177, 362-371 (2006).
28. Diebolder, C.A. et al. Complement is activated by IgG hexamers assembled at the cell surface. Science 343, 1260-1263 (2014).
29. Beum, P.V. et al. Complement activation on B lymphocytes opsonized with rituximab or ofatumumab produces substantial changes in membrane structure preceding cell lysis. J. Immunol. 181, 822-832 (2008).
30. Gorter, A. &Meri, S. Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol. Today 20, 576-582 (1999).
31. Min, X. et al. Expression and regulation of complement receptors by human natural killer cells. Immunobiology 219, 671-679 (2014).
32. Ramos, O.F., Sármay, G., Klein, E., Yefenof, E. &Gergely, J. Complement-dependent cellular cytotoxicity: lymphoblastoid lines that activate complement component 3 (C3) and express C3 receptors have increased sensitivity to lymphocyte-mediated lysis in the presence of fresh human serum. Proc. Natl. Acad. Sci. USA 82, 5470-5474 (1985).
33. Romain, G. et al. Antibody Fc engineering improves frequency and promotes kinetic boosting of serial killing mediated by NK cells. Blood 124, 3241-3249 (2014).
34. Bologna, L. et al. Ofatumumab is more efficient than rituximab in lysing B chronic lymphocytic leukemia cells in whole blood and in combination with chemotherapy. J. Immunol. 190, 231-239 (2013).
35. DiLillo, D.J. &Ravetch, J.V. Differential Fc-receptor engagement drives an anti-tumor vaccinal effect. Cell 161, 1035-1045 (2015).
36. Klaus, G.G., Pepys, M.B., Kitajima, K. &Askonas, B.A. Activation of mouse complement by different classes of mouse antibody. Immunology 38, 687-695 (1979).
37. Neuberger, M.S. &Rajewsky, K. Activation of mouse complement by monoclonal mouse antibodies. Eur. J. Immunol. 11, 1012-1016 (1981).
38. Bruhns, P. Properties of mouse and human IgG receptors and their contribution to disease models. Blood 119, 5640-5649 (2012).
39. Lim, S.H. et al. Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy. Blood 118, 2530-2540 (2011).
40. Vaughan, A.T. et al. Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalisation of CD20 independent of signalling via the cytoplasmic domain. J. Biol. Chem. jbc.M114.593806 (2015).
41. Frank, M., Walker, R.C., Lanzilotta, W.N., Prestegard, J.H. &Barb, A.W. Immunoglobulin G1 Fc domain motions: implications for Fc engineering. J. Mol. Biol. 426, 1799-1811 (2014).
42. Krissinel, E. &Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (2007).
43. Gaboriaud, C. et al. The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J. Biol. Chem. 278, 46974-46982 (2003).
44. Duncan, A.R. &Winter, G. The binding site for C1q on IgG. Nature 332, 738-740 (1988).
45. Idusogie, E.E. et al. Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc. J. Immunol. 164, 4178-4184 (2000).
46. Schneider, S. &Zacharias, M. Atomic resolution model of the antibody Fc interaction with the complement C1q component. Mol. Immunol. 51, 66-72 (2012).
47. Krapp, S., Mimura, Y., Jefferis, R., Huber, R. &Sondermann, P. Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J. Mol. Biol. 325, 979-989 (2003).
48. Lu, J. et al. Structure of FcγRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding. Proc. Natl. Acad. Sci. USA 112, 833-838 (2015).
49. Kennedy, A.D. et al. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J. Immunol. 172, 3280-3288 (2004).
50. Cartron, G. et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 99, 754-758 (2002).
51. Mancardi, D.A. et al. FcγRIV is a mouse IgE receptor that resembles macrophage FcϵRI in humans and promotes IgE-induced lung inflammation. J. Clin. Invest. 118, 3738-3750 (2008).
52. Kelton, W. et al. IgGA: a "cross-isotype" engineered human Fc antibody domain that displays both IgG-like and IgA-like effector functions. Chem. Biol. 21, 1603-1609 (2014).
53. Lee, C.-F., Paull, T.T. &Person, M.D. Proteome-wide detection and quantitative analysis of irreversible cysteine oxidation using long column UPLC-pSRM. J. Proteome Res. 12, 4302-4315 (2013).
54. Otwinowski, Z. &Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997).
55. Winn, M.D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D Biol. Crystallogr. 67, 235-242 (2011).
56. McCoy, A.J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
57. Adams, P.D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
58. Emsley, P., Lohkamp, B., Scott, W.G. &Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501 (2010).
59. Brünger, A.T. Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355, 472-475 (1992).
60. Chen, V.B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21 (2010).
61. Terwilliger, T.C. Maximum-likelihood density modification. Acta Crystallogr. D Biol. Crystallogr. 56, 965-972 (2000).
62. Liadi, I., Roszik, J., Romain, G., Cooper, L.J.N. &Varadarajan, N. Quantitative high-throughput single-cell cytotoxicity assay for T cells. J. Vis. Exp. 72, e50058 (2013).
63. Merouane, A. et al. Automated profiling of individual cell-cell interactions from high-throughput time-lapse imaging microscopy in nanowell grids (TIMING). Bioinformatics 31, 3189-3197 (2015).