Antigen Recognition, Immune Recptors, Antibody Structure, Isotypes and Function Flashcards
BCR
•The BCR is a membrane-bound immunoglobulin molecule that often detects 3- dimensional epitopes that are regions of intact macromolecules including proteins, lipids, nucleic acids, and carbohydrates.
TCR
•TCR are membrane-bound molecules whose epitopes are derived from proteins that have been proteolytically digested into peptide fragments (a string of adjacent amino acids), which are presented in the context of MHC molecules on another cell surface.
Variable Domains
- recognize the antigen and are unique to each receptor
- Within the V domains, sequence variability generates countless different receptors each able to recognize a unique antigen (repertoire diversity)
- The variability in the V domains is localized to three hypervariable protein loop areas called complementary determining regions (CDRs).
- The CDRs are located in the distal loops of the V domains that directly actually contact and bind the antigen.
Constant Domains
•conserved across different receptors, which anchor them to the cell membrane
An antibody molecule is composed of 4 different polypeptide chains: • [] Heavy chains (H) containing [] Variable (VH) and [] Constant (CH) domains. • [] Light chains (L) containing [] Variable (VL) and [] Constant (CL) domain.
An antibody molecule is composed of 4 different polypeptide chains: • 2 identical Heavy chains (H) containing 1 Variable (VH) and 3-4 Constant (CH) domains. • 2 identical Light chains (L) containing 1 Variable (VL) and 1 Constant (CL) domain.
The four chains (2 Heavy + 2 Light) are joined by [] to create a “Y” shaped antibody molecule comprised of three regions.
The four chains (2 Heavy + 2 Light) are joined by disulfide bonds to create a “Y” shaped antibody molecule comprised of three regions
Fab Region
- Abbreviation for: “fragment, antigen binding”
- Contains the entire light chain (with its single V and C domains) that is attached to the V and first C (VH and CH1) domains of the heavy chain
- Contains all of the components of the antibody that are involved with antigen binding
Fc Region
Abbreviation for: “fragment, crystalline”
- The remaining heavy chain C domains not included in the Fab make up the Fc
- Responsible for most of the biologic activity of the antibody molecule once antigen has been bound, and for transducing the signal from the Fab region to the cell upon antigen binding in membrane-bound BCR
Hinge Region
- Between the Fab and Fc
- Flexible linker that allows independent movement of the two antigen-binding Fab regions so they can each bind antigenic epitopes separated by various distances
- Can be a target for attack by microbial (bacterial) proteases that seek to destroy Ab molecules (e.g. IgA)
Heavy chains exist in 5 different forms [].
Heavy chains exist in 5 different forms (a, δ, ε, g, μ).
- Antibodies are assigned to different classes or isotypes: IgM, IgG, IgA, IgD and IgE based on which heavy chain they use.
- The IgG isotype is also subdivided into 4 subtypes (or allotypes), IgG1, IgG2, IgG3 and IgG4 based on antigenic differences of their heavy chains.
Light chains exist in 2 different forms [] that differ in their C regions.
Light chains exist in 2 different forms (κ and λ) that differ in their C regions.
•Both light chains can pair with any of the 5 types of heavy chains.
affinity
•The strength at which an antibody non-covalently binds an antigen is called the affinity – this is a measurement of single molecule of Ab interacting with a single epitope of an antigen.
Each IgG and IgE has [] antigen-binding sites.
Each IgG and IgE has 2 antigen-binding sites
IgA is secreted as a dimer, therefore has 4 antigen binding sites.
IgA is secreted as a dimer, therefore has 4 antigen binding sites.
IgM is secreted as a [], therefore has [] antigen binding sites.
IgM is secreted as a pentamer, therefore has 10 antigen binding sites.
avidity
The overall strength of antibody binding is called avidity, and is much greater than the affinity of a single antigen-binding interaction.
•monomer in serum, dimer in mucosa
allotypes
Allotypes are additional antigenic features of immunoglobulins that vary among individuals. The variation is due to polymorphic differences in the genes of L and H chains. Individuals may have different alleles at H or L loci
Idiotypes
Idiotypes are the antigenic determinants formed by the unique array of specific amino acids in the hypervariable region.
Anti-idiotypes
Anti-idiotypes refer to antibodies raised against idiotypic determinants. Antiidiotypes can be used in the clinic to specifically target some B cell malignancies.
Antigen Receptors: TCR
- T cells express a membrane-bound T cell receptor (TCR) which is a heterodimer composed of an a and b chain.
- Each of these chains contains a constant (C) and a variable (V) domain – similar to the immunoglobulin C and V domains in the light chain of the B cell receptor.
- Similar to the BCR, both the Va and Vb domains participate in TCR recognition of peptide antigen presented in the context of MHC molecules
TCR Variability Domain
- Within the V domains, sequence variability generates countless different receptors each able to recognize a unique antigen (repertoire diversity).
- The variability in the V domains is localized to three hypervariable areas called complementary determining regions (CDRs), which are located on the protruding loops of the TCR.
- The CDRs (particularly CDR3) are the areas within the V domains that actually bind the antigen.
TCRgδ
•Roughly 5-10% of the T cells express an alternative TCR composed of a g and δ chain (rather than ab). These cells are abundant in the epithelia and gut mucosa, and recognize (as yet incompletely defined) antigens presented by either non-classical MHC molecules, or without MHC at all. The gδ T cells appear to be much less diverse than the ab TCR population, are a part of an evolutionarily older (innate-like) immune system and are important in maintaining mucosal/epithelial integrity and/or healing and defense.
