Introduction to the MHC (structure and function) Flashcards

1
Q

what is MHC?

A

peptide receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what size peptide does MHC-I accommodate?

A

8-9 amino acid peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what size peptides does MHC-II accommodate?

A

13-25 amino acid peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the stability of MHC?

A

both MHC are instable when a peptide is not bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what type of cell is MHC-II always present on?

A

antigen presenting cells always have MHC-II on their surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what type of MHC do B cells express?

A

equally express MHC-I and MHC-II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what type of MHC do T cells express?

A

primarily MHC-I and sometimes MHC-II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what type of MHC do macrophages express?

A

Both MHC-I and MHC-II but more MHC-I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what type of MHC do dendritic cells express?

A

equally strong expression of both MHC-I and MHC-II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what type of MHC do epithelial cells of the thymus express?

A

MHC-I at low levels and MHC-II at high levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what type of cells express low levels of MHC-I but no MHC-II?

A

hepatocytes
Kidney cells
Brain cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what type of MHC do neutrophils express?

A

MHC-I strongly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what type of MHC do red blood cells express?

A

No MHC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the common domains of MHC-I and MHC-II protein structure?

A
  • Membrane-distal domains
  • Membrane-proximal domains (Ig fold structure)
  • Transmembrane segment
  • Cytoplasmia tail
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

where is the peptide binding groove found within both MHC-I and MHC-II?

A

in the membrane distal domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the membrane distal domains of MHC-I?

A

Alpha 1 and Alpha 2 subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are the membrane-proximal domains of MHC-I?

A

Alpha 3 and Beta 2 microglobulin subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what are the membrane distal domains of MHC-II?

A

Beta 1 and Alpha 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the membrane proximal domains of MHC-II?

A

Alpha 2 and Beta 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

where are most of the polymorphisms in MHC-II found?

A

In the beta 1 subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is the structure of the MHC-I peptide binding groove?

A

Found between the alpha 1 and alpha 2 domains, which are connected via protein beta sheets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is the structure of the MHC-II peptide binding groove?

A

Between the alpha 1 domains and beta 1 domain and is also connected via beta sheets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what mediates peptide binding to MHC?

A

anchor residues

24
Q

what can knock a protein out of the MHC binding groove?

A

Can be released (elluted) by acidic buffers (pH2-3)
- this makes the MHC very unstable

25
how are proteins eluted from the same MHC comparable?
Peptides eluted from the same MHC molecules show similar patterns in peptide sequence - they have distinct amino acid patterns
26
what is the different when short and long peptides bind in the MHC peptide binding groove?
Long peptides bulge when they bind Short peptides lie flat in the groove
27
what are anchor residues?
can be hydrogen bonds between the protein binding groove and the protein
28
what is the feature of MHC-I that means it binds smaller peptides?
MHC-I has conversed amino acid residues that bind the two ends of a peptide, meaning that it cannot be too long
29
why can MHC-II bind bigger peptides that MHC-I?
MHC-II lacks the conserved amino acid residues that MHC-I has, and so the peptide lies in an extending conformation within the peptide binding groove
30
what are polymorphisms?
mutations that have been selected for by evolution and are now distributed throughout the species
31
how is MHC genetically expressed?
codominantly
32
where are the majority of MHC polymorphisms found?
in the region that contacts the peptide
33
what is the role of Non-classical MHC-I?
acts as a stress ligand - binds to lipids and lipid like molecules
34
what MHC is important for stimulating natural killer cells?
MICA MICB - both types of non-classical MHC-I
35
what is the role of non-classical MHC CD1?
CD1 family allows presentation of glycolipids to NK-T cells
36
what is the affinity of MHC peptide interactions?
Low affinity
37
how does a T cell receptor recognize MHC?
T cell receptors recognise the MHC with peptide bound as a complex
38
how do peptides get presented on MHC-I?
Proteins are degraded into peptides within the cytoplasm and most are destined to be presented on MHC - the proteins a tagged by ubiquitin for destruction within the cell via the proteisome Cross-presentation also provides a source of protein to be expressed on MHC-I
39
what does cross-priming allow?
Exogenous protein to enter the MHC-I pathway
40
what are DRiPs?
Defective ribosomal products, also called primary translation products the result of improper RNA splicing, translation of frameshifts, improperly folded proteins, stalling ribosomes
41
how do DRiPs become expressed on MHC-I?
DRiPs are immediately degrade by the proteasome and so then can be expressed on MHC-I
42
what is a proteasome?
Protease complex present in the cytoplasm
43
what is the role of the proteasome?
Proteins are tagged for processing by the addition of the protein ubiquitin - proteins are then broken down into short peptides
44
what induces the immunoproteasome?
Interferons and alters processing of peptides
45
what is the function of the immunoproteasome?
increases protein cleavage after hydrophobic residues and decreased cleavage after acidic residues - this results in the generation of peptides able to be transported by TAP and with better terminal anchor residues for insertion into MHC-I
46
what are TAPs?
Transporter associated with Antigen Processing
47
what is the role of TAPs?
imports peptides into the ER
48
what are some examples of protein chaperones?
calnexin Calreticulin ERp57 tapasin
49
what is the role of chaperon proteins?
Maintain MHC-I structure in the absence of peptide
50
what is ERAAP?
Endoplasmic Reticulum Aminopeptidase associated with Antigen Processing
51
what is the function of ERAAP?
trims peptides to optimal length
52
what regulates ERAAP?
Upregulated by IFNg
53
what is MHC-II expression controlled by?
Master transcription factor CIITA
54
what is the role of master transcription factor CIITA?
ensures specific expression by antigen-presenting cells
55
what is the role of HLA-DM?
Binds to and stabilises empty MHC-II and catalyses the release of CLIP from MHC-II