T cells

Question 1

T cell antigen recognition

Answer 1

• T cells recognise huge diversity of different antigens
• each cell expreses a unique T cell receptor
• TCR is an aB heterodimer or yo heterodimer
• TCR recognises antigen as complex of antigen peptide fragment with self MHC molecule

Question 2

T cell receptor structure

Answer 2

• contains a variable region with antigen binding site, constant region, TM region, cytoplasmic tail
• receptor resembles membrane bound Fab fragment with 3 CDRs per chain
• one chain equivalent to light and one to the heavy chain of an antibody
• TCR binds antigen fragment and antigen presenting molecule

Question 3

TCR diversity

Answer 3

• aB and yo chains of TCR analogous to L and H chains of antibody
• TCR loci organised in similar way to immunoglobulin genes
• VJ rearrangement + C segment in a and y chain
• VDJ rearrangement + C segment in B and o chain (equivalent to heavy chain)
• same RSS sequence and the 12/23 rule
• recombinase enzyme catalyzes VJ/VDJ joining
• no somatic mutation in TCR genes (T cells have no AID)

Question 4

Why somatic mutation not found in T cellls

Answer 4

• T cells recognise antigen presented on cell surface
• self reactive T cells dangerous
• mutation could re-create them

Question 5

TCR complex

Answer 5

• TCR complex formed of antigen recognition proteins and invariant signal proteins (CD3)
• cytoplasmic TCR tail too short for signalling
• TCR signalling by clustering with CD3 and recruiting protein kinases to CD3 cytoplasmic tails
• CD3 is three dimers associated with recognition
• CD3 has ITAM sequences for docking of tyrosine kinases
• complementary charged residues between TCR and CD3 allow association
• TCR sends signals leading to different outcomes

Question 6

CD4/8 coreceptors

Answer 6

• T cells express one or the other (2 groups)
• CD4 has 4 Ig-like domains
• CD8 has a and B chains (heterodimer) each with 1 Ig-like domain
• CD4/8 bind to MHC molecules that present antigen to the T cell
• this helps the T cell to bind to the antigen presenting MHC and target it to specific cell types
• CD4 recognises MHC class 2 and CD8 class 1
• MHC presents antigen to the TCR

Question 7

CD8

Answer 7

• cytotoxic T cells

- MHC 1 found in all cells

Question 8

CD4

Answer 8

• helper T cells

- class 2 found in APCs

Question 9

T cell effectors

Answer 9

• contact other cells and induce change
• CD8 T cells recognise viral infection and kill it
• CD4 T cells contact macrophage, B cells, induce further response by cytokine secretion

Question 10

T cell Activation

Answer 10

• need antigen signal and co-stimulatory signal (protective)
• costimulatory molecules found on APCs
• they bind to CD28 on the T cell to activate it and induce IL-2
• amplification procedure lowers threshold of number of TCRs needed to be cross linked by MHC peptide complex
• CTLA-4 is inhibitory receptor for B7 molecules
• without infection APCs do not express costimulatory signal
• self reactive T cells escape negative selection in thymus are not activated

Question 11

Immunological Synpase

Answer 11

• at point of contact immunological molecules cluster
• diffusion in membrane to concentrate into focal points of interaction
• different protein sets segregated into synapse areas
  eg. c-SMAC: central supramolecular activation complex
  eg. p-SMAC: peripheral supramolecular activation complex

Question 12

T cell signalling

Answer 12

• clustering of TCR and co-receptor (CD4/8) initiates signalling by stimulating phosphorylation
• in resting T cell ITAMS of CD3 complex non-phosphorylated
• MHC binding to TCR leads to phosphorylation
• tyrosine kinase binds ITAMs and is phosphorylated itself

Question 13

Effector T cell Activation

Answer 13

• co-stimulatory signals NOT required for effector T cell activation
• IL-2 is cytokine needed for T cell proliferation
• IL-2 self-stimulates effector Th or Tc

Question 14

Helper T cells

Answer 14

• CD4
• no direct anti-pathogen effects but regulate other immune arms
• determine type of response by cytokine secretion
• Th1 cell recognises complex of bacterial peptide with MHC 2 and activates macrophage
• helper T cell recognises complex of antigenic peptide with MHC 2 to activate B cell
• classes result from activation and development in different cytokine environments

Question 15

Cytotoxic T cells

Answer 15

• CD8
• recognise antigens presented by MHC 1
• directly kill
• need IL-2 provided by T helper cells

Question 16

yo T cells

Answer 16

• 10% of T cells
• limited TCR repertoire
• high density in mucosal tissue
• tissue surveillance for stress/homeostasis
• recognise non peptide antigens
• binds antigen presented by non classical MHC
• cytotoxic
• most have no CD4/8

Question 17

yo receptor expression

Answer 17

• tissue specific
• express a receptor useful for dealing with pathogens from that site
• eg thymus predominantly has the Vo1 gene segment

Question 18

Phosphoantigens

Answer 18

• recognised by Vy9:Vo2 T cells
• phosphorylated intermediates of isoprenoid biosynthetic pathway (different antigen type) secreted by bacterium
• presented by CD277 (similar to B7 protein) to the Vy9:Vo2 receptor on T cells
• yo cell activation

Question 19

CD1

Answer 19

• presents lipid antigens and other hydrophobic antigens
• CD1: MHC 1 like H chains forming heterodimers with B2-microglobulin
• CD1 proteins non polymorphic
• deep hydrophobic groove for binding
• mycobacterial lipid antigens
• CD proteins recycle between membrane and vesicle membranes to present lipids to surface
• aB classes recognise CD1a/b/c
• yo recognise CD1d