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Sweet Rules: Linking Glycosylation to Antibody Function

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Antibody Glycosylation

Part of the book series: Experientia Supplementum ((EXS,volume 112))

Abstract

Antibodies produced upon infections with pathogenic microorganisms are essential for clearing primary infections and for providing the host with long-lasting immunity. Moreover, antibodies have become the most widely used platform for developing novel therapies against cancer and autoimmunity, requiring an in-depth understanding of how antibodies mediate their activity in vivo and which factors modulate pro- or anti-inflammatory antibody activities. Since the discovery that select residues present in the sugar domain attached to the immunoglobulin G (IgG) fragment crystallizable (Fc) region can modulate both, pro- and anti-inflammatory effector functions, a wealth of studies has focused on understanding how IgG glycosylation is regulated and how this knowledge can be used to optimize therapeutic antibody activity. With the introduction of glycoengineered afucosylated antibodies in cancer therapy and the initiation of clinical testing of highly sialylated anti-inflammatory antibodies the proof-of-concept that understanding antibody glycosylation can lead to clinical innovation has been provided. The focus of this review is to summarize recent insights into how antibody glycosylation is regulated in vivo and how select sugar residues impact IgG function.

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Abbreviations

ADCC:

Antibody-dependent cell-mediated cytotoxicity

Asp:

Asparagine

B4GALT1:

β-1,4-galactosyltransferase 1

BCR:

B cell receptor

CD:

Cluster of differentiation

CDC:

Complement-dependent cytotoxicity

CMP-SA:

Cytidine monophospho-sialic acid

ER:

Endoplasmic reticulum

Fab:

Fragment antigen binding

Fc:

Fragment crystallizable

FcαR:

Fc-alpha receptor

FcεR:

Fc-epsilon receptor

FcγR:

Fc gamma receptor

FcRn:

Neonatal Fc receptor

FNAIT:

Fetal or neonatal alloimmune thrombocytopenia

G0:

Agalactosylated

G1:

Monogalactosylated

G2:

Digalactosylated

GlcNAc :

N-acetylglucosamine

IFNγ:

Interferon gamma

Ig:

Immunoglobulin

IL:

Interleukin

ITAM:

Immunoreceptor tyrosine-based activation motif

ITIM:

Immunoreceptor tyrosine-based inhibitory motif

IVIg:

Intravenous immunoglobulin G

JC:

Joining chain

KA:

Association constant

Man:

Mannose

MBL:

Mannose-binding lectin

MHCII:

Major histocompatibility complex II

N:

Asparagine

NK cell:

Natural killer cell

PC:

Plasma cell

PNGaseF:

Peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase

RA:

Rheumatoid arthritis

SC:

Secretory component

ST6Gal1:

β-galactoside-α2,6-sialyltransferase 1

STAT6:

Signal transducer and activator of transcription 6

TCR:

T cell receptor

TD :

T cell-dependent

Tfh cell:

T follicular helper cell

Th cell:

T helper cell

TI:

T cell-independent

TNFα:

Tumor necrosis factor-alpha

Treg:

Regulatory T cell

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Acknowledgment

This manuscript was supported by funding from the German Research Foundation to F.N. (DFG FOR 2886, FOR 2953, NI711/9-1, and CRC1181-A07).

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  1. Chair of Genetics, Department of Biology, Institute of Genetics, University of Erlangen-Nürnberg, Erlangen, Germany

    Falk Nimmerjahn & Anja Werner

  2. Medical Immunology Campus Erlangen, Erlangen, Germany

    Falk Nimmerjahn

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Correspondence to Falk Nimmerjahn .

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    Marija Pezer

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Nimmerjahn, F., Werner, A. (2021). Sweet Rules: Linking Glycosylation to Antibody Function. In: Pezer, M. (eds) Antibody Glycosylation. Experientia Supplementum, vol 112. Springer, Cham. https://doi.org/10.1007/978-3-030-76912-3_12

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