Lecture 5

Question 1

Whats the basic structure of an antibody

Answer 1

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

Question 2

How was IgG discovered

Answer 2

By reducing the molecule and alkylating it

Question 3

What does the Fc part of the antibody do

Answer 3

It interacts with elements of the innate immune system (antigen elimination)

The FAB fragment can bind antigen divalently.

Question 4

What are the 5 classes of immunoglobulin and how do they differ

Answer 4

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

Question 5

What are the two classes of light chain

Answer 5

Kappa and Lambda (are not class restricted)

Question 6

What are myeloma proteins

Answer 6

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

Question 7

What are constant regions

Answer 7

Same for antibodies of a given H chain class or L chain type

Question 8

What are variable regions

Answer 8

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

Question 9

What are homologous domains

Answer 9

Regions of sequence homology identified. They’re made up of a series of domains. Cysteines are involved in intermolecular disulphide bond formation.

Question 10

What do homologous domains form

Answer 10

A series of globular domains - each stabilised by an intra-chain disulphide bond

Question 11

What is the folding pattern of the domains known as

Answer 11

The immunoglobulin fold

Question 12

What’s the structure of the immunoglobulin fold

Answer 12

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

Question 13

Features of the immunoglobulin gene super family

Answer 13

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.

Question 14

What does the variable region domain contain

Answer 14

3 hypervariable regions= complementary determining regions

Question 15

What are the interactions between antibody and antigen

Answer 15

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

Question 16

What do IgA and IgB contain

Answer 16

A single ITAM (immunoreceptor tyrosine activation motif) in their long cytoplasmic domain

Question 17

Structural basis of antibody diversity

Answer 17

• 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

Question 18

What are the early hypothesis of antibody diversity

Answer 18

-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

Question 19

When does diversity arise

Answer 19

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

Question 20

What was the dreyer and bennet hypothesis (1965)

Answer 20

Immunoglobulins are encoded by seperate C region and multiple V region genes

Question 21

What did Susumu Tonnegawa propose in 1976

Answer 21

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

Question 22

What are the 3 sets of immunoglobulin genes

Answer 22

-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

Question 23

What are heavy chains encoded by

Answer 23

3 segments of DNA called V, D and J