Introduction to the MHC (structure and function) Flashcards

1
Q

what is MHC?

A

peptide receptors

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2
Q

what size peptide does MHC-I accommodate?

A

8-9 amino acid peptides

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3
Q

what size peptides does MHC-II accommodate?

A

13-25 amino acid peptides

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4
Q

what is the stability of MHC?

A

both MHC are instable when a peptide is not bound

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5
Q

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

A

antigen presenting cells always have MHC-II on their surface

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6
Q

what type of MHC do B cells express?

A

equally express MHC-I and MHC-II

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7
Q

what type of MHC do T cells express?

A

primarily MHC-I and sometimes MHC-II

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8
Q

what type of MHC do macrophages express?

A

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

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9
Q

what type of MHC do dendritic cells express?

A

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

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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

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11
Q

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

A

hepatocytes
Kidney cells
Brain cells

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12
Q

what type of MHC do neutrophils express?

A

MHC-I strongly

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13
Q

what type of MHC do red blood cells express?

A

No MHC

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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
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15
Q

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

A

in the membrane distal domains

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16
Q

what are the membrane distal domains of MHC-I?

A

Alpha 1 and Alpha 2 subunits

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17
Q

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

A

Alpha 3 and Beta 2 microglobulin subunits

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18
Q

what are the membrane distal domains of MHC-II?

A

Beta 1 and Alpha 1

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19
Q

what are the membrane proximal domains of MHC-II?

A

Alpha 2 and Beta 2

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20
Q

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

A

In the beta 1 subunit

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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

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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

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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
Q

how are proteins eluted from the same MHC comparable?

A

Peptides eluted from the same MHC molecules show similar patterns in peptide sequence
- they have distinct amino acid patterns

26
Q

what is the different when short and long peptides bind in the MHC peptide binding groove?

A

Long peptides bulge when they bind
Short peptides lie flat in the groove

27
Q

what are anchor residues?

A

can be hydrogen bonds between the protein binding groove and the protein

28
Q

what is the feature of MHC-I that means it binds smaller peptides?

A

MHC-I has conversed amino acid residues that bind the two ends of a peptide, meaning that it cannot be too long

29
Q

why can MHC-II bind bigger peptides that MHC-I?

A

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
Q

what are polymorphisms?

A

mutations that have been selected for by evolution and are now distributed throughout the species

31
Q

how is MHC genetically expressed?

A

codominantly

32
Q

where are the majority of MHC polymorphisms found?

A

in the region that contacts the peptide

33
Q

what is the role of Non-classical MHC-I?

A

acts as a stress ligand
- binds to lipids and lipid like molecules

34
Q

what MHC is important for stimulating natural killer cells?

A

MICA
MICB - both types of non-classical MHC-I

35
Q

what is the role of non-classical MHC CD1?

A

CD1 family allows presentation of glycolipids to NK-T cells

36
Q

what is the affinity of MHC peptide interactions?

A

Low affinity

37
Q

how does a T cell receptor recognize MHC?

A

T cell receptors recognise the MHC with peptide bound as a complex

38
Q

how do peptides get presented on MHC-I?

A

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
Q

what does cross-priming allow?

A

Exogenous protein to enter the MHC-I pathway

40
Q

what are DRiPs?

A

Defective ribosomal products, also called primary translation products

the result of improper RNA splicing, translation of frameshifts, improperly folded proteins, stalling ribosomes

41
Q

how do DRiPs become expressed on MHC-I?

A

DRiPs are immediately degrade by the proteasome and so then can be expressed on MHC-I

42
Q

what is a proteasome?

A

Protease complex present in the cytoplasm

43
Q

what is the role of the proteasome?

A

Proteins are tagged for processing by the addition of the protein ubiquitin
- proteins are then broken down into short peptides

44
Q

what induces the immunoproteasome?

A

Interferons and alters processing of peptides

45
Q

what is the function of the immunoproteasome?

A

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
Q

what are TAPs?

A

Transporter associated with Antigen Processing

47
Q

what is the role of TAPs?

A

imports peptides into the ER

48
Q

what are some examples of protein chaperones?

A

calnexin
Calreticulin
ERp57
tapasin

49
Q

what is the role of chaperon proteins?

A

Maintain MHC-I structure in the absence of peptide

50
Q

what is ERAAP?

A

Endoplasmic Reticulum Aminopeptidase associated with Antigen Processing

51
Q

what is the function of ERAAP?

A

trims peptides to optimal length

52
Q

what regulates ERAAP?

A

Upregulated by IFNg

53
Q

what is MHC-II expression controlled by?

A

Master transcription factor CIITA

54
Q

what is the role of master transcription factor CIITA?

A

ensures specific expression by antigen-presenting cells

55
Q

what is the role of HLA-DM?

A

Binds to and stabilises empty MHC-II and catalyses the release of CLIP from MHC-II