Antigen Binding Receptors Flashcards
The 4 most important antigen binding receptors
PRR
BCR
TCR
Ig
BCR is found on..
B-Cells (even dividing)
Ig is found on…
Plasma cells
Immunoglobulins can be proteolytically cleaved by
Papain
Pepsin
Immunoglobulin structure
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
Isotype
Class!!
Type of heavy chain
Sub-isotype
Subclass!
aa difference within isotype
Allotype
Differences within individuals of the same species
Idiotype
Eptiope dependent differences
Igalpha/ Igbeta
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
Gene segment Rearrangement
- Genes in the heavy chain segment: V, D, J and C
- Removal of unwanted D and J gene segment
- Recombination of D and J exons- DJ recombo
- Removal of unwanted V and D gene segments
- Recombo of V and DJ exons- VDJ recombo
Structure of TCR
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)
TCR formation
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
Antibody and TCR diversity
- 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)
Genetic Basics of Antibody (BCR) Formation
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
Transposon
Integration of the transposon:
RAG1- RAG2 transposase gene
RSS (recombination signal) identification
Integration in the chondrichthyes
Isotype switching
Following B-cell activation
Begins with mature IgM and B-cell
Deletion until desired isotype
CDR1 and CDR2, how are they generated?
By POINT MUTATIONS after B-Cell activation.
Occurs parallel with isotype switching
Directed by cytokines of Th cells
How is CDR3 produced?
By VDJ (VJ on light chain) rearrangements
IgM and IgD are ONLY CDR3
Organisation of TCR Gene Families
3 gene families (in beta chain, but no segment D in alpha chain)
No point mutations after activation
No isotype switching
ONLY 1 CDR
Other options for variability of antigen binding receptors
- Junctional Diversity
- Receptor Editing
- Receptor rebuilding
- Somatic hypermutation and gene conversion
- Junctional diversity
During V(D)J reorganisation A few nucleotides stay between sections or fall out from minigens, if sections do not match after splicing
- Receptor Editing
After V(D)J reorganisation In the bone marrow How the autoreactive B-lymphocytes can redesign the BCR
- Receptor Rebuilding
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
