Antigen recognition

Question 1

does the innate response require proliferation?

Answer 1

no

Question 2

what is immune recognition driven by?

Answer 2

protein (antigen receptor) ligand (antigen) interactions

Question 3

what does antigen recognition involve?

Answer 3

somatically generated and clonally expressed T and B cell antigen receptors

Question 4

what are CDRs?

Answer 4

Complementarity-determining regions

Question 5

what are CDRs?

Answer 5

hypervariable parts of receptors which allow dor diversity in these receptors

Question 6

what are the two types of CDRs?

Answer 6

BCR and TCR

Question 7

describe the classical structure of Class 1 MHC heavy chain

Answer 7

• highly polymorphic anchored heavy chain (around 44kDa)
• three extracellular domains (A1,2,3)
• Transmembrane segment and a cytoplasmic tail
• A3 and B2 domain has cysteine residues for disulphide bonds
• alpha 1 &2 form a domain composed of two alpha helices which sits on top of 8 beta strands (this is most polymorphic region and forms peptide antigen binding cleft) - plays important role in Tcell receptor specific recognition
• b2m and A3 have folded structure due to disulphide bonds - these closely resemble similar domains of immunoglobulins - crucial in t cell induction through interaction with co receptors and co stimulating molecules
• b2m interacts with A1 and A2 domains to enhance peptide binding and stabilise overall MHC structure

Question 8

describe the light chain of MHC 1

Answer 8

light variant chain which is non-covalently attached to the heavy chain (it is a beta two microglobulin unit around 12kDa )

Question 9

what happens when T cell encounters MHC antigen?

Answer 9

• conformational change causes a shift and rotation of the variable domain to form a binding pocket to more closely matched the peptide
• LCK is then recruited to phosphorylate the ITAMS of CD3 recruiting ZAP70
• ZAP70 phosphorylates tyrosine residues of LAT, with a delay in Y132
• Additional components are recruited to the LAT signalosome initiating downstream signalling

Question 10

what can happen if an individual cannot mount an appropriate immune response??

Answer 10

a disease in the form of autoimmunity or hypersensitivity can result

Question 11

name some diseases that can occur due to disruption of HLA alleles and which ones?

Answer 11

DR2 - Narcolepsy, MS
DR4 - Rheumotoid Arthritis
DR3 - Graves’ disease

Question 12

MHC Class-1 presented peptides is a toll in vaccine design what has been developed and why?

Answer 12

• computer-aided methods have been developed to identify candidate peptides eg. deep-learning models that rank peptides binding affinities to MHC Class-1 molecules
  -these models are created to predict which peptides will have the highest binding affinity for the HLA alleles

Question 13

what does augmenting the antigenicity of a cytotoxic tcell epitope according to the MHC-peptide complex involve?

Answer 13

• involves replacement of AA within the sequence of a peptide epitope
• typically the MHC anchor residues or to alter the TCR-interacting residues within antigen peptide

Question 14

what does augmentation of antigens achieve?

Answer 14

by increasing the stability of the MHC-peptide-TCR complex the augmented antigens can achieve more potent immune responses

Question 15

give examples of augmenting MHC anchor residues

Answer 15

J Exp Med (2005) - replaced C with a V at the end of the sequence (V will now go into final binding pocket)

Question 16

name an experiment that focused on augmentation to affect the affinity of the MHC-peptide complex for TCR as oppose to the affinity of a peptide for MHC?

Answer 16

Slanksy et al. used mouse model to see immunisation with altered peptides
- showed that it wasn’t actually activating t cells that can go and target gene