Journal of Allergy and Clinical Immunology
Chapter 4Structure and function of immunoglobulins
Section snippets
The immunoglobulin domain: The basic immunoglobulin superfamily building block
Immunoglobulins belong to the eponymous immunoglobulin superfamily (IgSF).1, 2, 3 They consist of 2 heavy (H) and 2 light (L) chains (Fig 1), where the L chain can consist of either a κ or a λ chain. Each component chain contains one NH2-terminal variable (V) IgSF domain and 1 or more COOH-terminal constant (C) IgSF domains, each of which consists of 2 sandwiched β-pleated sheets pinned together by a disulfide bridge between 2 conserved cysteine residues.1 Each V or C domain consists of
Immunoglobulin gene organization and rearrangement
Immunoglobulin heavy and light chains are each encoded by a separate multigene family,9, 10 and the individual V and C domains are each encoded by independent elements: V(D)J gene segments for the V domain and individual exons for the C domains. The primary sequence of the V domain is functionally divided into 3 hypervariable intervals termed complementarity-determining regions (CDRs) that are situated between 4 regions of stable sequence termed framework regions (FRs; Fig 1).
H chain C domain structure and function
In general, the C domain of the H chain defines effector function, whereas the paired V domains of the antibody confer antigenic specificity. The H chain constant domain is generally defined as CH1-CH2-CH3 (IgG, IgA, and IgD), with an additional domain (CH4) for IgM and IgE. As described above, the CH1 domain is located within the F(ab) region, whereas the remaining CH domains (CH2-CH3 or CH2-CH4) comprise the Fc fragment. This Fc fragment defines the isotype and subclass of the immunoglobulin.
FcγR
FcRs for immunoglobulin link the humoral immune compartment to the cellular immune compartment. The net result of binding of immunoglobulin to receptor is a function of the receptor, the cell on which it is expressed, and any ancillary signals. Tight regulation of binding to the FcR is necessary to maintain a healthy immune system.
The most extensively studied FcRs are the IgG-binding receptors, termed FcγR. In human subjects 3 classes of FcγR have been identified: I, II, and III. FcγRII and
Immunoglobulin transport
The transport of polymeric immunoglobulin into mucosal secretions is a function of the polymeric immunoglobulin receptor (pIgR). This receptor is found on the basolateral surface of epithelial cells lining the mucosal surface. Membrane-bound pIgR consists of 5 immunoglobulin-like domains (extracellular portion) with a transmembrane and cytoplasmic domain. pIgA (with the J-chain) binds to the pIgR on the epithelial cell. It is then internalized and transcytosed to the apical cell membrane. The
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Disclosure of potential conflict of interest: H. W. Schroeder receives research support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the United States Immunodeficiency Network, and NABI Pharmaceuticals and is a councilor for the Henry Kunkel Society. L. Cavacini is a consultant for GTC Biotherapeutics and receives research support from the National Institutes of Health.