Antigen Binding Receptors

Question 1

The 4 most important antigen binding receptors

Answer 1

PRR
BCR
TCR
Ig

Question 2

BCR is found on..

Answer 2

B-Cells (even dividing)

Question 3

Ig is found on…

Answer 3

Plasma cells

Question 4

Immunoglobulins can be proteolytically cleaved by

Answer 4

Papain

Pepsin

Question 5

Immunoglobulin structure

Answer 5

Y-shaped
Has a domain structure where one domain contains around 110 aa’s
Full size: 160 kDa
4 peptide chains with disulfide bridges
2 identical glycosylated heavy chains weighing 55kDa- alpha, gamma, delta, epsilon, mu
2 identical, non-glycosylated light chains weighing 25kDa: kappa and lamda

Question 6

Isotype

Answer 6

Class!!

Type of heavy chain

Question 7

Sub-isotype

Answer 7

Subclass!

aa difference within isotype

Question 8

Allotype

Answer 8

Differences within individuals of the same species

Question 9

Idiotype

Answer 9

Eptiope dependent differences

Question 10

Igalpha/ Igbeta

Answer 10

Signalling molecules!!!
Stretch into the cytosol
Are near the BCR
Detect changes in the Fc
Phosphorylation activates them
ITAM: immunoreceptor tyrosine based activating motif
ITIM: immunoreceptor tyrosine based inhibitory motif

Question 11

Gene segment Rearrangement

Answer 11

1. Genes in the heavy chain segment: V, D, J and C
2. Removal of unwanted D and J gene segment
3. Recombination of D and J exons- DJ recombo
4. Removal of unwanted V and D gene segments
5. Recombo of V and DJ exons- VDJ recombo

Question 12

Structure of TCR

Answer 12

Antigen combination site is on the variable region (Valpha and Vbeta)
Calpha and Cbeta (constant)
Hinge
Transmembrane region- on surface of T-cells
Cytoplasmic tail

(I think instead of alpha and beta can be gamma and delta too)

Question 13

TCR formation

Answer 13

Is responsible for recognising antigen peptide fragments bound to MHC molecules
Has 1 variable and 1 constant chain
Are heterodimers- this increases their variability
Most are alpha beta, some are gamma delta
They have only one CDR ( compatibility determining region)
Families are the same as the antibody families
No mutation after activation, no isotype switching

Question 14

Antibody and TCR diversity

Answer 14

• Multiple genes and reorganisations
• Interchain recombinations, crossing overs, point mutations (only Abs)
• Potential number of variations: AB=10 (to the power of 16) , TC=10 (to the power of 9)

Question 15

Genetic Basics of Antibody (BCR) Formation

Answer 15

3 gene family: kappa, lamda and heavy chain
All 3 families are segmented

V= variability
D= Diversity- only on the heavy chain
J=Joining
C=Constant- isotypes are different

Fab: 10 to the power of 16 variations and point mutations

Question 16

Transposon

Answer 16

Integration of the transposon:
RAG1- RAG2 transposase gene
RSS (recombination signal) identification
Integration in the chondrichthyes

Question 17

Isotype switching

Answer 17

Following B-cell activation
Begins with mature IgM and B-cell
Deletion until desired isotype

Question 18

CDR1 and CDR2, how are they generated?

Answer 18

By POINT MUTATIONS after B-Cell activation.
Occurs parallel with isotype switching
Directed by cytokines of Th cells

Question 19

How is CDR3 produced?

Answer 19

By VDJ (VJ on light chain) rearrangements

IgM and IgD are ONLY CDR3

Question 20

Organisation of TCR Gene Families

Answer 20

3 gene families (in beta chain, but no segment D in alpha chain)
No point mutations after activation
No isotype switching
ONLY 1 CDR

Question 21

Other options for variability of antigen binding receptors

Answer 21

1. Junctional Diversity
2. Receptor Editing
3. Receptor rebuilding
4. Somatic hypermutation and gene conversion

Question 22

1. Junctional diversity

Answer 22

During V(D)J reorganisation
A few nucleotides stay between sections or fall out from minigens, if sections do not match after splicing

Question 23

2. Receptor Editing

Answer 23

After V(D)J reorganisation
In the bone marrow 
How the autoreactive B-lymphocytes can redesign the BCR

Question 24

3. Receptor Rebuilding

Answer 24

After V(D)J reorganisation
A few mature, activated B-lymphocytes can edit their receptors to allow for a more specific antigen binding in the secondary lymphoid tissue

Question 25

4. Somatic Hypermutation and Gene Conversion

Answer 25

After V(D)J reorganisation
Random mutation in receptor of mature, activated B-lymphocytes which means a more specific antigen binding in the secondary lymphoid tissue 
Uses AID, UNG and APE1 enzymes

Question 26

Uniqueness of these enzymes: AID, UNG, APE1

Answer 26

Take part in:

1. Somatic hypermutation
2. Gene conversion
3. Isotype switching