Lecture 6 - Antigen Presentation

Question 1

Compare Antigen Recognition in B/T-cells?

(2 Points)

Answer 1

BCR/Antibodies - can interact with ‘naked’ antigens or antigens in naked state

TCRs - antigens need to be presented in a complex with an MHC molecule

Question 2

Define :
(i) Polygenic
(ii) Polymorphic

Answer 2

(i) Encoded by Several different MHC Class I and II genes (>200 in humans)
(ii) Multiple Allelic Variants of each gene within population (individuals are typically heterozygous)

Question 3

Compare the Structures of MHC Class I and II Molecules

(2 Points)

Answer 3

• MHC Class I - consists of single chain of immunoglobulin-like domains, with non-covalently associated second chain
• MHC Class II - consists of two chains of immunoglobulin-like domains

Question 4

Define the two types of T-cell co-receptor, and the MHC class they recognise

Answer 4

• CD4 - recognise MHC Class II
• CD8 - recognise MHC Class I

Question 5

How do the MHC Classes differ in terms of peptide binding?

Answer 5

MHC Class I - tend to bind to peptides at their ends
MHC Class II - tend to bind peptides along their length

Question 6

Compare the Expression of MHC Classes on the surface of different cell types

(4 Points)

Answer 6

• T-cells - high expression of MHC Class I only
• APCs (e.g., B-cells, Macrophages, DCs) - high expression of both MHC I and II
• Nucleated cells - express varying degress of MHC I
• Non-nucleated cells - do no express any MHC I/II

Question 7

How do MHC Classes vary in Peptide Loading?

(2 Points)

Answer 7

• Class I - load peptides from pathogens that have infected expressing cell
• Class II - load peptides from pathogens killed by the cell or in the local environment

Question 8

Compare the cellular location of peptide loading for MHC Class I and II

(2 Points)

Answer 8

• Class I - self/foreign antigens are loaded from the ER lumen
• Class II - foreign antigens are loaded in acidified vesicles following displacement of the CLIP

Question 9

What is the role of the invariant chain (Li) in Class II Processing?

(2 Points)

Answer 9

• Targets delivery of MHC II to appropriate endosomal compartment via Cytoplasmic tails
• Prevents Premature binding of self/other peptides to MHC II peptide-binding groove during synthesis in ER

Question 10

What is the role of HLA-DM in Class II Processing?

(2 Points)

Answer 10

• Catalyse peptide loading of MHC II by triggering release of CLIP, facilitating the binding of other peptides
• Does this by binding and unbinding to MHC II, stabilising the empty conformation to allow foreign peptide binding (binds more strongly than CLIP)

Question 11

Define which type of APC is specialised to present a particular antigen type

(3 Points)

Answer 11

• Dendritic Cells - self-antigens, protein antigens that trigger allergic responses, viral/bacterial antigens
• Macrophages - intracellular bacterial antigens
• B-cells - soluble antigens

Question 12

State the Two Signals required to stimulate naive T-cells to proliferate and differentiate

(Give Example)

Answer 12

• Ligation of TCR and CD4/CD8 Co-receptor to MHC complex
• Co-stimulatory signal e.g., B7 Complex of APC which is recognised by the CD28 receptor

Question 13

What is the Purpose of Adjuvants?

(2 Points)

Answer 13

• Some Proteins may fail to induce immune response because they fail to elicit co-stimulatory signals in APCs
• Mixing them with Bacteria/Bacterial proteins makes them immunogenic (adjuvant) and therefore more likely to elicit co-stimulatory signals