Antibody molecules can be divided into distinct classes and sub classes on the basis of differences in the structure of their heavy chain C regions. The classes (also called isotypes) of antibody molecules are named IgA, IgD, IgE, IgG, and IgM (Table 1). In humans, IgA and IgG classes can be further subdivided into closely related subclasses, or subtypes, called IgA1 and IgA2 and IgG1, IgG2, IgG3, and IgG4. (Mice, which are often used in the study of immune responses, differ from humans in that the IgG class is divided into the IgG1, IgG2a, IgG2b, and IgG3 sub classes; certain strains of mice lack the gene for IgG2a but produce a related subclass called IgG2c.) The heavy-chain C regions of all antibody molecules of one class or subclass have essentially the same amino acid sequence. This sequence is different in antibodies of other classes or subclasses. Heavy chains are designated by the letter of the Greek alphabet corresponding to the class of the antibody: IgA1 contains α1 heavy chains; IgA2, α2; IgD, δ; IgE, ε; IgG1, γ1; IgG2, γ2; IgG3, γ3; IgG4, γ4; and IgM, µ. In human IgM and IgE antibodies, the C regions contain four tandem Ig domains (see Fig. 1). The C regions of IgG, IgA, and IgD contain only three Ig domains. These domains are generically designated CH domains and are numbered sequentially from the amino terminus to the carboxy terminus (e.g., C_H1, C_H2, and so on). For each antibody subclass, these regions may be designated more specifically (e.g., Cγ1, Cγ2 for different IgGs).

Table1. Human Antibody Classes (Isotypes)

Fig1. Structure of an antibody molecule. (A) Schematic diagram of a secreted immunoglobulin G (IgG) molecule. The antigen-binding sites are formed by the juxtaposition of VL and VH domains. The heavy-chain C regions end in tail pieces. The locations of complement- and Fc receptor–binding sites within the heavy chain constant regions are approximations. (B) Schematic diagram of a membrane-bound IgM molecule on the surface of a B lymphocyte. The IgM molecule has one more CH domain than IgG has, and the membrane form of the antibody has C-terminal transmembrane and cytoplasmic portions that anchor the molecule in the plasma membrane. (C) Structure of a human IgG molecule as revealed by x-ray crystallography. In this ribbon diagram of a secreted IgG molecule, the identical heavy chains are colored blue and red so that they can be easily visualized, although they are identical, and the light chains are colored green; carbohydrates are shown in gray. (Courtesy Dr. Alex McPherson, University of California, Irvine.)

Different classes and subclasses of antibodies perform different effector functions. The reason for this is that most of the effector functions of antibodies are mediated by the binding of heavy-chain C regions to Fc receptors (FcRs) on different cells, such as phagocytes, NK cells, and mast cells, and to plasma proteins, such as complement proteins. Antibody classes and subclasses differ in their C regions and therefore in what they bind to and what effector functions they perform. The effector functions of each antibody class are listed in Table 1 .

Antibody molecules are flexible in their hinge regions, permitting them to bind to different arrays of antigens. As discussed earlier, every antibody contains at least two antigen binding sites, each formed by a pair of VH and VL domains. Many Ig molecules can orient these binding sites so that two antigen molecules on a planar (e.g., cell) surface may be engaged at once (Fig.2). This flexibility is conferred, in large part, by the hinge region located between C_H1 and C_H2 in certain antibody classes. The hinge region varies in length from 10 to more than 60 amino acid residues in different antibody classes. Portions of this sequence assume an unfolded and flexible conformation, permitting molecular motion between the C_H1 and C_H2 domains. Some of the greatest differences between the constant regions of the IgG subclasses are concentrated in the hinge. This leads to different overall shapes of the IgG subclasses.

Fig2. Flexibility of antibody molecules. The two antigen-binding sites of an immunoglobulin (Ig) monomer can simultaneously bind to two determinants separated by varying distances. In (A), an Ig molecule is depicted binding to two widely spaced determinants on a cell sur face; in (B), the same antibody is binding to two determinants that are close together. This flexibility is mainly due to the hinge regions located between the C_H1 and C_H2 domains, which permit independent movement of antigen-binding sites relative to the rest of the molecule.

There are two classes, or isotypes, of light chains, called κ and λ, that have distinct carboxy-terminal constant (C) regions. Each antibody molecule has either two identical κ light chains or two identical λ light chains but never one of each. In humans, about 60% of antibody molecules have κ light chains, and about 40% have λ light chains. Marked changes in this ratio can occur in patients with B-cell tumors because the many neo plastic cells, being derived from one B-cell clone, produce a single species of antibody molecules, all with the same light chain. In fact, an abnormal predominance of either κ-bearing cells or λ-bearing cells is often used clinically for the diagnosis of B-cell lymphomas. In mice, κ-containing antibodies are about 10 times more abundant than λ-containing antibodies. In contrast to heavy-chain classes, there are no known differences in function between κ-containing antibodies and λ-containing antibodies.

Secreted and membrane-associated antibodies differ in the amino acid sequence of the carboxy-terminal end of the heavy chain C region. The secreted form, found in blood, mucosal secretions, and other extracellular fluids, contains a carboxy-terminal hydrophilic region called the tail piece. The membrane bound form of antibody contains a carboxy-terminal stretch that includes two segments: a hydrophobic α-helical transmembrane region, followed by an intracellular tail, which contains a juxtamembrane positively charged region of three amino acids (Fig.3). The positively charged amino acids, sometimes called a stop-transfer sequence, bind to negatively charged phospholipid head groups on the inner leaflet of the plasma membrane and help anchor the protein in the membrane. In membrane IgM and IgD molecules, the cytoplasmic portion of the heavy chain is short (only three amino acid residues in length). In membrane IgG and IgE molecules, the tail is approximately 30 amino acid residues in length and contains a signaling motif that contributes to memory B-cell activation.

Fig3. Membrane and secreted forms of immunoglobulin (Ig) heavy chains. The membrane forms of the Ig heavy chains, but not the secreted forms, contain transmembrane regions made up of hydrophobic amino acid residues and cytoplasmic domains that differ significantly among the different antibody classes. The cytoplasmic portion of the membrane form of the µ chain and the δ chain contains only three residues, whereas the cytoplasmic region of IgG and IgE membrane heavy chains (membrane γ and ε heavy chains) contains 20–30 residues. The secreted forms of the antibodies end in C-terminal tail pieces, which also differ among classes: µ has a long tail piece (21 residues) that is involved in pentamer formation, whereas IgGs have a short tail piece (3 residues).

Secreted IgG and IgE and all membrane Ig molecules, regard less of class, are monomeric with respect to the basic antibody structural unit (i.e., they contain two heavy chains and two light chains). In contrast, the secreted forms of IgM and IgA form multimeric complexes in which two or more of the four chain core antibody structural units are covalently joined. IgM is secreted mainly as pentamers but also some hexamers of the core four-chain structure, whereas IgA is usually secreted as a dimer. These complexes are formed by noncovalent interactions between the tail pieces that are located at the carboxy-terminal ends of the secreted forms of µ and α heavy chains (see Table1). Multimeric IgM and IgA are further stabilized by an additional non-Ig 15-kDa polypeptide called the joining (J) chain, which is disulfide bonded to the tail pieces of the Ig C regions and serves to stabilize the multimeric complexes and to trans port multimers across epithelial cells from the basolateral to the luminal end. As we will see later, multimeric forms of antibodies bind to antigens more avidly than monomeric forms.

Antibodies from different species differ in the C regions and in framework parts of the V regions. Therefore, when Ig molecules from one species are introduced into another (e.g., horse serum antibodies or mouse monoclonal antibodies injected into humans), the recipient sees them as foreign, mounts an immune response, and makes antibodies against the introduced Ig.

Smaller sequence differences are present in antibodies from different individuals even of the same species, reflecting inherited polymorphisms in the genes encoding the C regions of Ig heavy and light chains. When polymorphic forms of an immunoglobulin found only in some individuals of a species can be recognized by antibodies, the sequences that differ among individuals are called allotypes, and the antibody that recognizes an allotypic variation is called an anti-allotypic antibody. Some differences are concentrated in the CDRs and constitute the idiotypes of antibodies. An antibody that recognizes some aspect of the CDRs of another antibody is therefore called an anti-idiotypic antibody. There have been interesting theories that individuals produce anti-idiotypic antibodies against their own antibodies that control immune responses, but there is little evidence to support the importance of this potential mechanism of immune regulation.

اخر الاخبار

اخبار العتبة العباسية المقدسة

إقامة مسابقة (مرفأ النور) العلمية للمشاركات في فعاليات ملتقى الكوثر بنسخته الثالثة

ضمن ملتقى الكوثر الثالث.. ورشة تسلط الضوء على بناء الوعي القرآني لدى النساء

شعبة فاطمة بنت أسد (عليها السلام): ملتقى الكوثر منصةً لتحقيق وعي أسري مستند للقرآن الكريم

شعبة فاطمة بنت أسد (عليها السلام) تطلق النسخة الثالثة من ملتقى الكوثر

المزيد

الآخبار الصحية

طريقة مبتكرة للكشف المبكر عن أمراض القلب والشرايين

منظمة الصحة تحذر من خطر إدمان الشباب لأكياس النيكوتين

خبراء يحذرون من عادة شائعة تهدد صحة الملايين

خبير يكشف 5 حقائق طبية صادمة وغير معروفة

المزيد

الآخبار التكنلوجية

الأولى في العالم.. الصين تجري تجربة رائدة في الفضاء باستخدام "جنين اصطناعي"

دراسة حديثة تفند ربط التستوستيرون بالمخاطرة لدى الرجال

ميتا تضيف وضع "المحادثة المخفية" إلى تطبيق "واتساب"

فوبيا المرتفعات ليست من الدماغ.. دراسة تكشف السبب

المزيد

مواضيع ذات صلة

Monoclonal Antibodies

Structural Features of Antibody Variable Regions

General Features of Antibody Structure

Stages of T-Cell Maturation

Mechanisms that Limit Innate Immune Responses

Stimulation of Adaptive Immunity

Systemic and Pathologic Consequences of Inflammation

Immuno microscopy

V(D)J Recombination

Role of Macrophages in Tissue Repair

Ingestion and Killing of Microbes by Activated Phagocytes

Sequence of Events in Inflammation: Vascular Changes and Leukocyte Migration Into Tissues