Lecture 7 Antibodies and genetic diversity

Question 1

What are antibody isotypes

Answer 1

The various classes and subclasses of the H and L chains of the immunoglobulins

Question 2

What are antibody allotypes

Answer 2

Inherited sequence variations in heavy chain genes found in individual members of the species (immunoglobulin of one individual may differ from another individual of same species)

Question 3

What are antibody idiotypes

Answer 3

Structural variations in the immunoglobulin resulting from variations in AA sequences of variable domains of H and L chains

Question 4

What are the three genes of light chains

Answer 4

Variable (V), Joining (J) and constant (C)

Question 5

What are the fourgenes of heavy chains

Answer 5

Variable (V), Joining (J), Diversity (D) and constant (C)

Question 6

How do you make a complete Antigen-binding site

Answer 6

Light chain joins one V to one J gene

Heavy chain joins one V to one D to one J gene

Question 7

Describe the kappa light (kL) chain (3)

Answer 7

kL chain has one (C) and two variable regions (V & J)
30 - 41 different V, 5 J and one C gene
Any kL chain produced will have any one C, V and J region hence there may be 200 possible kL combinations

Question 8

Describe the assembly and expression of kL chain

Answer 8

The specific V gene is joined up with desired J gene, the J genes after the desired one and the C region in a single exon. The undesired J genes are then spliced out to form a single V, J and C kL chain.

Question 9

Describe the lambda light chain

Answer 9

Lambda has one constant (C) and two variable regions (V and J)
30-40 different V, 5 J and 6-9 C regions
Any lambda chain will have any one C, V and J
Many combinations

Question 10

Describe assembly and expression of lambda chain

Answer 10

Unlike kL J and C are inbetween in eachother because many Cs
Firstly desired V combines with desired J and rest are deleted.
VJ then joins with the C that was on the right of the desired J

Question 11

Describe the Heavy chain

Answer 11

Nine heavy chain isotypes (C)
45 different V, 6 J genes and 23 different D genes
6210 differnt combinations

Question 12

Describe assembly and expression of heavy chains

Answer 12

Firstly the desired D and J join and rest of D and Js deleted.
Then the V joins the DJ and rest of V deleted
The C can be either Cm (IgM) or Cd (IgD), splicing then occurs to give a singular VDJC(m or d)

Question 13

How can a person produce so many different antibody molecules

Answer 13

When a light chain and heavy chain pair for an antigen binding site their is a large number of possible combinations (2.3 million)
Additional diverisity comes from base deletions and insertions and by somatic mutations
End result (1x10 x 16)

Question 14

What is heavy chain isotype switch

Answer 14

When the VDJ is assembled the nearest C molecule is Cm (IgM) with other C isotypes further down chain. To express the other isotypes, a specific DNA deletion process occurs so the desired isotype is the nearest C molecule to the VDJ.

Question 15

How is the heavy chain isotype switch completed

Answer 15

Looping out enables isotype switch. The DNA is ‘looped’ so the desired genes are out of the way and the desired C gene is adjacent to the VDJ genes. The loop is then cut away so the desired VDJC is produced

Question 16

What immunoglobulin classes have multiple heavy chain isotypes and what are they called

Answer 16

IgG - (gamma 1,2,3,4)
IgA - (alpha 1 & 2)
Igm (m) , IgE (e) and IgD (d) have one heavy chain isotope.