Antigen Recognition by T Cells Flashcards
Discuss the differences between recognition of antigens by T and B cells
B cells recognise antigens directly, to fight extracellular microbes
T cells don’t recognise antigen directly, instead they recognise APCs. Designed to fight intracellular microbes
Describe the antigen recognition by T cells
Most T cells (αβ TCRs) recognise cell-bound Ags (peptides), but γδ T cells recognise Ags that aren’t peptides.
APCs only process FOREIGN Ags into peptides which bind MHC and then presented on APC surface
CD4+ recognise Ags by MHCII
CD8+ cytotoxic recognise Ags by MHCI
What are the types of APCs and what type of cells do they present to?
Dendritic cells: only APC to present to naïve T cells
Macrophages: present to prev activated CD4+ (Th1)
B cells: previously activated CD4+ (Th2)
CD8+ T cells recognise Ags displayed by regular nucleated cells too, not just APCs. Can also recognise Ags from microbes that have escaped from phagosome (Cross presentation)
Dendritic cells are a type of APC. Describe these cells and the signals they send for naive t cell activation
Signal 1: Ag recognition on APC. Not enough to activate T cell
Signal 2, costimulation: Binding costimulatory molecules (B7 family e.g.CD80/CD86) on APC to costimulatory CD28 TCR.
Signal 1 AND 2 = activates naïve T cells
APCs exposed to infection increase B7 + MHC expression
What is a third type of signal sent by dendrtitic cells during T cell activation?
Signal 3: cytokines produced by APCs (after infection)
Differentiate activated T cells into various effector T cells to ensure most suitability:
IL-12= differentiates to Th1.
IL-4= differentiates to Th2
Th1= macrophage cooperation. Th2= B cells + eosinophil/mast cooperation
Describe how B cells can also become APCs and the effect of Th2
B cells internalise protein Ags and present to effector CD4+ T cells (Th2), activating them.
Th2 cells provide signals to help B cells that:
-Regulate class switch (e.g. IFNy and IgG; IL4 and IgE)
-Affinity maturation
How do T cells recognise antigens?
Descrbe the structure of TCRs, and mention the variable domains
T cells recognise antigens by TCR:
2 chains: α and β (most TCRs), but also γ and δ
Each chain has 1 variable and 1 constant domain (V & C)
Antigen binding site= Vα + Vβ
V and C domains of TCR and BCR are homologous
In variable domains, AA sequence varies highly between different TCR; each V domain contains 3 hypervariable regions
How can TCRs be so diverse?
TCRs expressed by different T cells are v diverse
~10^10 different TCR allow casi infinite Ag recognition
This is generated by re-arrangement of gene segments when T cells develop in the thymus
(VDJ rearrangement for Vβ and VJ rearrangement for Vα)
Describe MHCs- what do they present to and what are they composed of?
MHC I: present to CD8+ T cells. Composed of α chain + B2-microglobulin. All nucleated cells (top diagram)
MHC II: present to CD4+ T cells. Composed of α+B chain. APCs only, not all nucleated cells (bottom diagram)
γδ T cells recognise Ags not displayed by MHC I and II (not MHC restricted)
MHCs are also known as HLAs. Describe these
Human MHC molecules = HLA (human leucocyte Ags)
MHC I: HLA-A, B, C; *E, *F, *G
MHC II: HLA-DP, DQ, DR; *DM, *DO
*less polymorphic, have diff functions (not just peptide presentation)
Explain the binding grooves, what they are formed by and how this helps T cell activation
MHCI peptide binding groove formed by 2 alphas
MHCII peptide binding groove formed by a + B
So MHC can hold peptide such that T cell can make contact
CD4/CD8 bind to MHC away from Ag peptide binding groove
CD4/CD8 binding decreases T cell activation threshold: T cells can make contact w less peptide:MHC complexes for activation
Describe the exogenous antigen processing and presentation pathway
Exogenous Ags are taken up in cells, processed and presented by MHC II to CD4+ T cells
Exogenous Ags are phagocytosed + eliminated by Abs (neutralisation, opsonisation, complement)
CD4+ T effectors help macrophages (Th1) and B cells (Th2) eliminate extracellular bacteria
Explain the process by which extracellular Ags (e.g. bacteria) is taken up in cells, processed and presented by MHC II to CD4+ T cells
APC processes extracellular proteins into lysosomal vesicles
It makes and transports MHCII to endosomes
MHCII needs algo in groove to hold it juntos =invariant chain in groove until at endosome
At the endosome a small bit of chain remains (CLIP) and then HLA-DM takes it out so peptide can make MHC complex
Peptide:MHC complex formed + expressed on surface
Describe the endogenous (cytosolic) antigen processing and presentation pathway (MHC I and CD8+ T cells)
Cytosolic Ags (e.g. viruses, mutated proteins) are presented by MHC I to CD8+ T cells:
Virus proteins tagged w ubiquitin recognised by proteasome and broken down into peptides
Peptides move into ER via TAP
In ER hay newly formed MHCI w empty groove
MHC1 stabilised w peptide-> to Golgi->into exocytic vesicle. Complex expressed
If both MHC I and MHC II are produced and assembled in ER how come MHC II can’t load peptides that derive from cytosolic pathogens (viruses) and MHC I can’t load peptides that derive from phagocytosed extracellular pathogens?
MHCII= associated w invariant chain = blocks groove of MHCII → prevents loading of peptides transported by TAP from cytosol into ER
Peptides for MHC II aren’t transported to ER but are located in late endo-lysosomal vesicles; only MHCII can reach these vesicles!!
This is segregation and if disrupted: no activated CTLs for viruses/cancers. You’d lack CD4+ for killing bacteria.
