Structure of B and T Lymphocyte Receptors Flashcards
what do B cell receptors contain?
- an antibody of defined specificity
what do T cell receptors contain?
- structure that resembles part of an antibody molecule (Fab fragement) that is specific for peptides from the antigen that was presented to the naive T lymphocyte by the APC
what is the structure of B-cell receptors?
quaternary protein with two identical heavy chains and two identical light chains
what are co-receptors and what are some examples?
BCRs cannot signal directly when they bind an antigen so to transmit activation signals into the cell they use co-receptors
- Igα and Igβ
- CD19/CD21/CD81
explain how lignand receptor binding causes molecular changes?
dimerization or multimerization occurs and the receptors are clustered and localized in lipid rafts
what are the two antibody forms?
membrane bound form and secreted Ig form
what produces antibodies?
B lymphocytes and plasma cells
what are plasma cells?
highly differentiated B lymphocytes that are specialized in the secretion of antibodies
what is the structure of the typical antibody molecule IgG?
- divalent
- two binding sites for cross linking
- proline rich hinge region that allows an extension
- 2 identical light and 2 identical heavy chains
- held together by disulfide bonds
- contains variable and constant domains
what are the two light chains and what are the five heavy chains?
- kappa and lambda
- mu, alpha, gamma, delta and epsilon
compare the amino acid sequences for the variable region and the constant region?
- variable region: the amino acid sequences of the
antibody molecules produced by different clones of B lymphocytes VARY - constant region: identical amino acid sequence even when different clones of B lymphocytes produce antibody molecules.
what is the difference between the C terminal and N terminal of a typical antibody molecules (IgG)?
- N terminal: antigen binding site/recognition site (Fab)
- C terminal: mediates effector activities (Fc, c=crystallization)
what is a paratope?
the structure of the Fab fragment of an ANTIBODY that makes direct contact with an antigen
what is an epitope?
the portion of the ANTIGEN that is bound to the antibody
how many hypervariable regions are there in the heavy and light chains of an antibody?
3 on each
the residues in the hypervariable region make?? what is another name for the hypervariable region?
- the closest contact with antigen at the antigen combing sites
- complementary determining region
what does the amino acid sequence in the complementary determining regions determine?
shape, charge and chemistry of an antibody for its antigen ie specificity
describe antigen-antibody interactions
- non-covalent bonds
- reversible
- require close steric fit
- closer fit= tighter fit= higher affinity binding specificity
what is affinity?
the strength of an individual bond for a certain interaction between antibody and antigen
what is avidity?
combined strength of binding of multiple interactions (multivalent)
for T cell receptor complexes with coreceptors what is the functions of CD3, CD4 and 8 and CD28?
- CD3 contains ITAMs that transmits signals to the cell
- CD4 and CD8 increase the avidity
- CD28 engages CD80/86 on the antigen presenting cell to activate the T cell
what are the 5 immunoglobulins?
- IgG
- IgA
- IgM
- IgD
- IgE
what is the heavy chain and light chain composition of secreted IgG?
heavy chain: gamma
light chain: kappa or lambda
what are some specific properties of secreted IgG?
- monomer
- crosses the placenta (protects fetus only in womb)
- found in the blood stream and tissue fluid
what are the functions of secreted IgG?
- agglutinates
- precipitates
- opsonizes ***
- mediates ADCC ***
- activates complement
- neutralizes
what is the heavy chain and light chain composition of IgM?
heavy chain: mu
light chain: kappa or lambda
junction chain
what are some specific properties of IgM?
- pentamer
- found in serum and intravascular spaces
- H chain has extra CH4 domain
where is the membrane form of IgM expressed and what does it do?
- expressed on cell surface of early B cells as a monomer to serve as a B cell receptor
what is the first immunoglobulin produced in infants and in an immune response?
IgM
which antibody is the most efficient antibody for agglutination and complement fixation?
IgM
what are some functions of IgM?
- agglutinates
- activates complement
- provides early protection
- produced in responce to T independant antigens
- low affinity
- poor neutralization
what is the heavy chain and light chain composition of IgD?
heavy chain: delta
light chain: kappa or lambda
what are some specific properties of IgD?
- monomer
- it is surface bound on mature B cells and not secreted
which immunoglobulin is used as a signal receptor?
IgD
which immunoglobulin triggers further differentiation of B lymphocytes?
IgD
what is the heavy and light chain composition of IgA?
heavy chain: alpha
light chain: kappa or lambda
j chain
secretory side piece
what are some specific properties of IgA?
- dimer
- found in external secretions
- absorbed through the intestinal lumen
what are the functions of IgA?
- agglutinates
- neutralizes
what are the steps of IgA transport?
- IgA dimer binds to poly-Ig receptor on the internal surface
- IgA receptor transported across vesicles
- vesicle fuses with membrane on the external side
- cleave secretory piece to release IgA
what are some specific properties of IgE?
- monomer
- H chains have extra CH4 domains in which they bind to IgE receptors on basophils and mast cells
- lowest concentration compared to all other antibodies
what is the heavy chain and light chain composition of IgE?
heavy chain: epsilon
light chain: kappa or lambda
what are some specific activities of IgE?
- protects against parasitic infections
- associated with allergies or hypersensitivities
- its a reaginic antibody (gives us allergies)
- binds to IgE Fc receptors on basophils, eosinophils and mast cells causing degranulation
what is a variable region?
the amino acid sequences of antibody molecules produced by different clones of B lymphocytes vary
what is a constant region?
it has an identical amino acid sequence even when different clones of B lymphocytes produce antibody molecules
what is the antigen independent phase ?
stem cells —-> pro B/T cells —-> pre B/T cells ——-> immature B/T cells —-> mature B/T cells with BCR/TCR
- generates a vast repertoire of B/T cells with receptors of different specificity
what are the mechanisms used by B cells to produce their vast repertoire?
- selection of many mini-gene segments
- recombination
- addition and deletion
- association of many different heavy and light chains to form binding sites
what are mini genes?
- recombination of gene segments to create different possible antigen binding sites
what are the mini segments of mini genes?
- variable (V)
- diversity (D)
- joining (J)
what are the mini gene segments that make up light chains and heavy chains?
- L chains: V + J
- H chains: V + D + J
what is the 12/23 rule?
recombination signal sequences that direct recombination have a nonamer and heptamer sequence separated by a 12 or 23 basepair spacer sequence where a 12 bp RSS MUST pair with a 23 bp RSS for recombination to occur
what joins the gene segments and how?
RAG1/2 recombinase encoded by the RAG gene recognizes and cuts DNA at the immunoglobulin coding region and the RSS
where are the 3rd hypervariable regions located (CDR3)?
junction of V-J and D-J
what is allelic exclusion?
is the process by which only one allele of a gene is expressed while the other allele is silenced.
why is allelic exclusion important?
- this mechanism ensures that a single B cell expresses one specific type of B cell receptor (BCR), or a single T cell expresses one specific type of T cell receptor (TCR). It prevents the production of receptors with mixed specificities, which would dilute the immune response and reduce its effectiveness.
what are the different chain assortments for TCR?
- different beta chains and alpha chains pair for TCRab
- different delta chains pair with gamma chains for TCRgd
what are somatic hypermutations and when do they occur?
- introduction of point mutations in the V region of rearranged H and L chains
- occur on B cells after encountering antigen
what can happen after a somatic hypermutation?
affinity maturation
