Schematic structure of an<unk> : two heavy chains (blue, yellow) and the two light chains (green, pink). The antigen binding site is circled.<unk> es are heavy (~150 kDa) proteins of<unk> out 10 nm in size, arranged in three globular regions that roughly form a Y shape. In humans and most mammals, an<unk>  unit consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds.<unk> ch chain is a series of domains: somewhat similar sequences of<unk> out 110 amino acids<unk> ch. These domains are usually represented in simplified schematics as rectangles. Light chains consist of one variable domain VL and one constant domain CL, while heavy chains contain one variable domain VH and three to four constant domains CH1, CH2, ... Structurally an<unk>  is also partitioned into two antigen-binding fragments <unk> , containing one VL, VH, CL, and CH1 domain<unk> ch, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape. In between them is a hinge region of the heavy chains, whose flexibility allows<unk> es to bind to pairs of epitopes at various distances, to form complexes (dimers, trimers, etc.), and to bind effector molecules more<unk> sily. In an electrophoresis test of blood proteins,<unk> es mostly migrate to the last, gamma globulin fraction. Conversely, most gamma-globulins are<unk> es, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ. This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ heavy chains which characterize the IgG class of<unk> es. Antigen-binding site The variable domains can also be referred to as the FV region. It is the subregion of<unk>  that binds to an antigen. More specifically,<unk> ch variable domain contains three hypervariable regions – the amino acids seen there vary the most from<unk>  to<unk> . When the protein folds, these regions give rise to three loops of β-strands, localized near one another on the surface of the<unk> . These loops are referred to as the complementarity-determining regions (CDRs), since their shape complements that of an antigen. Three CDRs from<unk> ch of the heavy and light chains together form an<unk> -binding site whose shape can be anything from a pocket to which a smaller antigen binds, to a larger surface, to a protrusion that sticks out into a groove in an antigen. Typically however only a few residues contribute to most of the binding energy. The existence of two identical<unk> -binding sites allows<unk>  molecules to bind strongly to multivalent antigen (repeating sites such as polysaccharides in bacterial cell walls, or other sites at some distance apart), as well as to form<unk>  complexes and larger antigen-antibody complexes. The resulting cross-linking plays a role in activating other parts of the immune system. The structures of CDRs<unk> ve been clustered and classified by Chothia et al. and more recently by North et al. and Nikoloudis et al. However, describing an<unk> 's binding site using only one single static structure limits the understanding and characterization of the<unk> 's function and properties. To improve<unk>  structure prediction and to take the strongly correlated CDR loop and interface movements into account,<unk>  paratopes should be described as interconverting states in solution with varying probabilities. In the framework of the immune network theory, CDRs are also called idiotypes. According to immune network theory, the adaptive immune system is regulated by interactions between idiotypes. Fc region The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the<unk> <unk>  region binds to an antigen. Effector cells (such as macrophages or natural killer cells) bind via their Fc receptors (FcR) to the Fc region of an<unk> , while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway. Another role of the Fc region is to selectively distribute different<unk>  classes across the body. In particular, the neonatal Fc receptor (FcRn) binds to the Fc region of IgG<unk> es to transport it across the placenta, from the mother to the fetus.<unk> es are glycoproteins, that is, they<unk> ve carbohydrates (glycans) added to conserved amino acid residues. These conserved glycosylation sites occur in the Fc region and influence interactions with effector molecules. Protein structure The N-terminus of<unk> ch chain is situated at the tip.<unk> ch immunoglobulin domain<unk> s a similar structure, characteristic of all the members of the immunoglobulin superfamily: it is composed of between 7 (for constant domains) and 9 (for variable domains) β-strands, forming two beta sheets in a Greek key motif. The sheets create a "sandwich" shape, the immunoglobulin fold, held together by a disulfide bond.<unk>  complexes complexes that bind to multiple antigen molecules. Secreted<unk> es can occur as a single Y-shaped unit, a monomer. However, some<unk>  classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six units).<unk> es also form complexes by binding to antigen: this is called an antigen-antibody complex or immune complex. Small antigens can cross-link two<unk> es, also leading to the formation of<unk>  dimers, trimers, tetramers, etc. Multivalent antigens (e.g., cells with multiple epitopes) can form larger complexes with<unk> es. An extreme example is the clumping, or agglutination, of red blood cells with<unk> es in the Coombs test to determine blood groups: the large clumps become insoluble, leading to visually apparent precipitation. B cell receptors The membrane-bound form of an<unk>  may be called a surface immunoglobulin (sIg) or a membrane immunoglobulin (mIg). It is part of the B cell receptor (BCR), which allows a B cell to detect when a specific antigen is present in the body and triggers B cell activation. The BCR is composed of surface-bound IgD or IgM<unk> es and associated Ig-α and Ig-β heterodimers, which are capable of signal transduction. A typical human B cell will<unk> ve 50,000 to 100,000<unk> es bound to its surface. Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate the BCRs from most other cell signaling receptors. These patches may improve the efficiency of the cellular immune response. In humans, the cell surface is bare around the B cell receptors for several hundred nanometers, which further isolates the BCRs from competing influences.
Antibody
Microantibody
Heterophile antibody
Antigen
Isoantibodies
Immune complex
Autoantibody
Immunogen