7 - B and T Cell Receptors Flashcards
Structure of B and T cell receptors
- Alpha and beta chains
- Variable region (antigen binding site, top of receptor)
- Constant/fc region (effector function, bottom of receptor)
Long chains
Heavy chains
Short chains
Light chains
B-1 cells
- B-1a and B-1b
- Arise in foetal liver
- T independent antigens
B-2 cells
- Marginal zone and follicular
- Arise in bone marrow
- T dependent antigens
B cell classes
- B-1 cells
- B-2 cells
- Regulatory B cell
What is the first antibody that appears on a developing B cell
IgM
Ig expression during B lymphocyte maturation
- Mature B lymphocytes activated by antigens and other stimuli differentiate into plasmablasts and then into antibody secreting plasma cells
- Process is accompanied by changes in pattern of Ig production
Changes in pattern of Ig production
- Increased production of the secreted form of Ig relative to the membrane form
- Expression of Ig heavy chain isotypes other than IgM and IgD, by heavy chain isotype (or class) switching
- Introduction of new amino acid substitutions into the variable domains of the antibody heavy and light chains to create high-affinity antibodies (affinity maturation)
Antibodies/Immunoglobulins (Ig)
- Secreted form of the B cell receptor
- Consists of 2 heavy chains (H) and 2 light chains (L)
- Light chain may be κ or ƛ
(never both) - H and L chains include constant (invariant) C
domains and variable V
domains - Greatest variation in the
antigen binding domains of H and V chains
HV1, 2, and 3
Hypervariability regions in V domains
Antigen-antibody complexes
- An antigen can cross-link two
antigen-binding sites to create antigen-antibody complexes - Possible due to flexible antibody arms
T cell classes
- CD8 cytotoxic T cells
- CD4 Th1 cells
- CD4 Th2 cells
- CD4 Th17 cells
- Tfh cells
- CD4 regulatory cells
CD8 cytotoxic T cells
Kill virus infected cells (some intracellular bacteria)
CD4 Th1 cells
- Activate infected macrophages
- Provide help to B cells for antibody production
- Targets microbes that persist in macrophage vesicles and extracellular bacteria
CD4 Th2 cells
- Provide help to B cells for antibody production, especially switching to IgE
- Target helminth parasites
CD4 Th17 cells
- Enhance neutrophil response
- Promote barrier integrity (skin, intestine)
- Target Fungi
Tfh cells
- B cell help
- Isotype switching
- Antibody production
- Target all pathogens
CD4 regulatory T cells
Suppress T cell responses
Fab fragment and TCR
- Both disulphide linked heterodimer
- Each chain contains one Ig C domain and one Ig V domain
Ig vs TCR
TCR are anchored to cell membrane and are not produced in secreted form
How to T cells see antigens
Unlike B cells and antibodies which can recognise antigens in their native form, T cells (via their TCR) can only see antigen as short peptides bound to MHC molecules
Structure of ⍺β T cell receptor
- The TCR heterodimer is composed of two transmembrane glycoprotein chains, ⍺ and β
- Each chain includes a variable V region and a constant C region, a stalk,a transmembrane region and
cytoplasmic domains
How do CD8 T cells recognise antigen
- CD8 Cytotoxic T lymphocytes recognise target cells that display peptide fragments of non self proteins bound to MHC class 1 molecules at the cell surface
- MHC class 1 molecules are expressed by all nucleated cells in the body
- Peptides from intracellular pathogens, especially viruses, are recognised by CTL and result in the infected cell being killed by apoptosis
Class of MHC that CD8 recognises
Class 1
Class of MHC that CD4 recognises
Class 2
How do CD4 T cells recognise antigen
CD4 T cells recognise peptides resulting from antigen degradation within intracellular vesicles, displayed on the cell surface in the context of MHC class 2 molecules
How are CD4 T cell subsets defined
On basis of the cytokines they secrete and on their functions
MHC Class 1
- MHC encoded HLA-A, -B, -C heavy chain α bound to β2-microglobulin
- The α chain folds into 3 domains: α1, α2, α3
- The α1 and α2 domains form the antigen binding groove
- Peptides (8-10 aa long) are stabilised at both ends of the groove by binding to invariant sites
MHC Class 2
- Class 2 molecules (HLA-DP, DQ, DR in humans) heterodimers of α and β chain
- No β2-microglobulin
- Peptides are at least 13 aa long
- Ends are not bound to groove, peptide is held in place by interactions along its length
Human MHC genes
- Highly polymorphic
- Each MHC locus has many alleles (variant genes that occupy the same loci and encode variants of the MHC protein)
- The expressed MHC molecule determines which peptide antigen the cell can bind and present for surveillance by CD4 and CD8 T cells
Allelic variation in MHC molecules
- Occurs at specific sites
- variation arising from genetic polymorphism is usually in the peptide binding clefts
- Such variation can alter the specificity of an MHC molecules for a peptide antigen
How do CD4 T cells help activate B cells
Via germinal centre reaction
γδ T cell receptor
- Specialised to bind to certain ligands, including heat shock proteins and non peptide ligands such as mycobacterial lipid antigens
- May not be restricted by classical MHC class 1 and 2 molecules
- May bind to free antigen and/or may bind to peptides presented by non classical MHC
