Lecture 5 Flashcards
Whats the basic structure of an antibody
Light chain = 25kd
Heavy chain =50kd
Y shaped, two arms and a tail region. Y structure is made of four polypeptide chains linked by a disulphide bond
How was IgG discovered
By reducing the molecule and alkylating it
What does the Fc part of the antibody do
It interacts with elements of the innate immune system (antigen elimination)
The FAB fragment can bind antigen divalently.
What are the 5 classes of immunoglobulin and how do they differ
They differ in the amino acid sequence of their heavy chains.
IgG: main class in serum and tissues (important in secondary responses)
IgM: important in primary responses
IgA; in serum and secretions protects mucosal surfaces. It’s found in tears, salivia and milk
IgD: don’t know much about it
IgE: present at low levels in secreted form, involved in protection against parasites and allergy
What are the two classes of light chain
Kappa and Lambda (are not class restricted)
What are myeloma proteins
Cancer of plasma cells - a single plasma cell divides out of control because it divides from a single cell- it can be isolated from the blood
What are constant regions
Same for antibodies of a given H chain class or L chain type
What are variable regions
They bind to antigen, they differ between antibodies with different specificities.
These correspond to the end terminal regions and allow the production of different antibodies
What are homologous domains
Regions of sequence homology identified. They’re made up of a series of domains. Cysteines are involved in intermolecular disulphide bond formation.
What do homologous domains form
A series of globular domains - each stabilised by an intra-chain disulphide bond
What is the folding pattern of the domains known as
The immunoglobulin fold
What’s the structure of the immunoglobulin fold
C domain has 7 beta strands (two layers) and V domain has 9 beta strands
Beta strands by all domains are divided by loop regions.
Each domain is made of beta cleated sheets, stabilised by intra straining disulphide bonds
Features of the immunoglobulin gene super family
Its generally involved in recognition, binding and adhesion. There are more than 700 members in the human genome.
Domains can be V-like or C-like.
What does the variable region domain contain
3 hypervariable regions= complementary determining regions
What are the interactions between antibody and antigen
Non-covalent (electrostatic interactions, hydrogen bonds, van der waals forces, hydrophobic interactions)
They’re individually weak but if many form simultaneously, the antibody: antigen interaction is specific and high affinity
What do IgA and IgB contain
A single ITAM (immunoreceptor tyrosine activation motif) in their long cytoplasmic domain
Structural basis of antibody diversity
- Heavy chain generally contributes more to antigen binding is more variable than the light chain
-Variations in the sequence length of CDRs are the main determinants of antibody diversity
-CDR3 tend to be the most variable in length and sequence
What are the early hypothesis of antibody diversity
-Must be enough genes to encode for these
-Somatic mutation, B cells that code for these antibodies can be mutated
-Somatic recombination, genes that code for antibodies are made of pieces that can recombine when cells develop
When does diversity arise
Arises by somatic recombination and mutation of a limited number of antibody genes inherited gene segments from our parents which make up the V regions
What was the dreyer and bennet hypothesis (1965)
Immunoglobulins are encoded by seperate C region and multiple V region genes
What did Susumu Tonnegawa propose in 1976
Immunoglobulin genes are rearranged during b cell development.
Single constant region gene multiple variable region genes in the germ line. When B cells are differentiating, this undergoes rearrangement
What are the 3 sets of immunoglobulin genes
-Heavy chains found on chromosome 14
-Kappa chains found on chromosome 2
-Lambda chains on chromosome 22
Each locus has multiple variable region genes and one or a few constant region genes
What are heavy chains encoded by
3 segments of DNA called V, D and J
