MHC - Antigen Presentation

Question 1

T cells can only recognise peptides antigens presented by BLANK

Answer 1

T cells can only recognise peptides antigens presented by MHC molecules

MHCs (Major Histocompatibility Complexes) also known as HLAs (Human Leukocyte Antigens)

Question 2

MHC genes are highly polymorphic

TRUE OR FALSE

Answer 2

TRUE

MHC polymorphism is focused in the peptide binding site

Question 3

T cells only ‘see’ peptides exhibited on a defined framework

TRUE OR FALSE

Answer 3

TRUE

Question 4

Class I and II MHC molecules present similar/different types of peptides

Answer 4

Class I and II MHC molecules present DIFFERENT types of peptides

Peptide side chains fit in MHC pockets

Question 5

There are several HLA (MHC) class I and II genes, what are they:

Answer 5

All nucleated cells express several types of Class I molecules on their cell surface:
HLA-A, HLA-B and HLA-C

Specialised antigen-presenting cells also express additional Class II molecule:
HLA-DR, HLA-DQ and HLA-DP

Each individual possesses two variants of each HLA molecule type

NOTE: These are all highly polymorphic

There are more types, but they don’t bind peptides: HLA-DM, HLA-DO, HLA-E, HLA-F, HLA-G

Question 6

MHC expression is the same across all cell types

TRUE OR FALSE

Answer 6

FALSE
Differential MHC expression on different cell types.
e.g. Thymic epithelium heavily expresses Class II, also expresses class I (Applied in T cell development negative selection (aka MHC restriction)

Question 7

How do Class I and Class II MHC capture different sets of peptides?

Answer 7

Class I MHC alerts T cells to intracellular infections e.g. viruses or tumour antigens:

• class I MHC is expressed on almost all cells
• captures peptides from endogenous antigens
• displays them to T cells that express the CD8 co-receptor

In contrast, Class II MHC alerts T cells to extracellular infections e.g. bacteria:

• class II MHC is expressed only on dendritic cells, B cells & some macrophages
• captures peptides from exogenous antigens
• displays them to T cells which express the CD4 co-receptor

Class I and II MHC molecules capture peptides from different cellular compartments

Question 8

Antigen Presentation by Class I MHC molecules:

Answer 8

Cytosolic peptides (produced by the specialized immunoproteasome) are delivered to the ER lumen by Transporter Associated with antigen Processing (TAP) proteins

The peptide loading complex (PLC) orchestrates class I MHC assembly in the ER:

The ‘first draft’ peptide is edited by an aminopeptidase (ERAAP)

Question 9

Class I MHC molecules capture peptides in the BLANK

Answer 9

Class I MHC molecules capture peptides in the Endoplasmic Reticulum (ER)

Question 10

Antigen Presentation by Class II MHC molecules:

Answer 10

Phagocytosis, Macro-pinocytosis and Receptor-mediated Endocytosis drives antigen capture

Cathepsins in MIIC-endosome are only activated by acidity

Cathepsins degrade invariant chain

Antigen capture is boosted by inflammatory signals (e.g. PAMPs)

TLR activation transiently enhances the uptake of soluble antigens, immune complexes and phagocytosable forms of antigens:

Question 11

How do newly synthesised MHC Class II molecules reach the lysosomal compartment in an ‘empty’ state?

Answer 11

Need to prevent newly synthesised, unfolded self proteins from binding to immature MHCs.

Invariant chain (CLIP fragment) stabilises MHC Class II by non-covalently binding to the immature MHC Class II molecule and forming a nonomeric complex

Question 12

How are exogenous peptides generated and loaded onto MHC-II complexes in the lysosomal compartment if the Invariant chain is still present?

Answer 12

1. Endo-lysosomal proteases (e.g. Cathepsins)
2. HLA-DM catalyses ejection of CLIP and aids optimal peptide selection
3. Successful peptide capture triggers export to cell surface

Question 13

Endo-lysosomal proteases perform two key roles:

Answer 13

1. generate peptides from antigen

2. initiate cleavage of Invariant chain (leaving CLIP fragment in place)

Question 14

Cross-presentation of extracellular antigens by Class I MHC molecules:

Answer 14

Cross-presentation is the presentation of exogenous antigens on class I MHC, an important exception to the rule that only endogenous antigens appear on class I MHC.

Cross-presentation involves the cytosolic diversion of endocytosed exogenous antigens.

Question 15

Antigen recognition by B Lymphocytes:

Answer 15

B cells and the antibodies they make can recognise virtually any chemical structure, unlike T cells, which can only recognize short peptides presented by MHC molecules.

Follicular dendritic cells (FDCs) [ FDCs ARE NOT DENDRITIC CELLS!!!] in lymphoid follicles capture and store opsonised antigens on their cell surface

B cells use mechanical force to extract antigens from FDCs

Question 16

Dendritic cells report on infections at distant sites

TRUE OR FALSE

Answer 16

TRUE

Question 17

APCs deliver 3 kinds of signals to naive T cells:

Answer 17

Activation
Survival
Differentiation

Question 18

Which of Class I/II have a closed off end?

Answer 18

Class I MHCs have a closed off end

Class II MHCs have a more open end

Question 19

MHC-1 prefers to present [LONG/SHORT] peptides with [BASIC/ACIDIC] / [HYDROPHOBIC/HYDROPHILIC] residues at ends.

Answer 19

MHC-1 prefers to present SHORT peptides with

BASIC/ HYDROPHOBIC residues at ends.