MHC Flashcards

1
Q

How do you describe genetically similar organisms or tissues?

A

Syngeneic

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2
Q

How do you describe genetically dissimilar organisms or tissues of the same species?

A

Allogeneic

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3
Q

What genes encode antigens?

A

HLA genes in humans
H2 genes in mice

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4
Q

What is the function of the major histocompatibility complexes?

A

Essential for recognition of peptide antigens by T cells

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5
Q

Which chromosome are human HLA genes located on?

A

Chromosome 6

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6
Q

Which chromosome are mice H-2 genes located on?

A

Chromosome 17

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7
Q

What genes are found in Class III region?

A

Genes encoding immune regulatory molecules = tumour necrosis factor, C3-5 complement proteins and heat shock proteins

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8
Q

How are MHC alleles expressed?

A

Codominantly = both are expressed so you get a combined phenotype

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9
Q

Define locus

A

Physical position on chromosomes where genes are found

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10
Q

Describe allele

A

Variant of particular polymorphic gene in the population

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11
Q

Define polymorphism

A

Variation of a specific DNA sequence

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12
Q

Define haplotype

A

Subset of all alleles on a specific chromosome in the population

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13
Q

Define diplotype

A

Subset of all genotypes on homologous chromosome pairs in the population

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14
Q

What determines the degree of polymorphism/?

A

Determined by the number of alleles at each locus

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15
Q

Are MHC genes polymorphic?

A

Highly

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16
Q

What does an individual carry up to 6 of?

A

Individual carries up to 6 different Class I MHCs

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17
Q

What is the structure of Class I MHC?

A

Hetrotrimeric complex = heavy chain, light chain and peptide antigen

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18
Q

What is the Class I heavy chain made of?

A

3 alpha glycoprotein domains = transmembrane protein

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19
Q

Which domains make up the Class I peptide binding groove?

A

Alpha 1 & 2

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20
Q

What makes up the light chain?

A

Beta 2 microglobulin

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21
Q

Where are the genes that encode the b2m of Class I MHC?

A

The genes are outside the MHC region

22
Q

How many amino acids long can Class I peptide groove bind?

A

8-10 amino acids

23
Q

Why do Class I MHC bind smaller peptide antigens?

A

Their MHC groove has closed ends and the antigen has to fit wholly into the bowl

24
Q

Can Class I MHC bind a variety of similar peptides?

A

Yes, because only specific parts of the antigen are registered

Ony 2-3 amino acids anchor the peptide to the MHC

25
Q

What activates MHC molecules?

A

Binding of antigen

26
Q

What is the structure of Class II MHC?

A

Heterotrimeric complex = alpha-chain, beta-chain and peptide antigen

27
Q

Which domains make up the Class II peptide binding groove?

A

Alpha 1 & Beta 1

28
Q

Describe Class II MHC binding groove?

A

Open ended

29
Q

How many amino acids long can Class II MHC bind?

A

13-17

30
Q

Which cells express Class I MHC?

A

All nucleated cells (not RBCs)

31
Q

Which cell express Class II MHC?

A

Only expressed in APC

32
Q

Name APCs

A

T cells
B cells
Dendritic cells
Macrophages
Thymic epithelial cells

33
Q

When can non-APCs express Class II MHCs?

A

Inflammatory conditions

34
Q

What role does TCR recognizing MHC-peptide complex play?

A

T cell development and activation

35
Q

Why can one person’s T cells not recognize antigens presented on another person’s MHC?

A

Because people have different MHC types

36
Q

Where are Class I MHC found?

A

Mainly in the cytosol of any cell and are presented to cytotoxic T cells leading to cell death

37
Q

Where are Class II MHC found?

A

In endocytic vesicles of APCs and are presented to helper T cells

38
Q

What effects can B cell activation cause?

A

Secretion of antibodies to eliminate extracellular bacteria/toxins

39
Q

What effect can macrophage activation cause?

A

Killing of intra vesicular bacteria and parasites

40
Q

Where are proteosomes found?

A

Cytosol

41
Q

Which part of proteosomes recognize ubiquitin?

A

19S regulatory cap

42
Q

Where are TAP1/2 proteins found?

A

ER membrane

43
Q

What is the function of TAP1/2 proteins?

A

Transport viral peptides from cytosol onto Class I MHC molecules in the ER

44
Q

Where does ATP bind on TAP1/2 proteins?

A

ABC domain = ATP-binding cassette

45
Q

How are Class I MHC assembled?

A

Partly folded alpha chain binds to calnexin until beta 2 microglobulin binds

Released from calnexin and binds chaperone proteins = calreticulin and Erp57

46
Q

How do Class I MHC present antigens?

A

Class I MHC bind to TAP via tapasin

Cytosolic proteins are degraded to peptide fragments by proteasome

TAP delivers peptides to Class I MHC = completing its folding

Fully loaded Class I MHC is released from TAP complex and exported

47
Q

What does the partly folded alpha chain of Class I MHC bind?

A

Calnexin

48
Q

What are the two charperone proteins Class II MHC binds?

A

Calreticulin and Erp57

49
Q

What allows Class I MHC to bind to TAP?

A

Tapasin

50
Q

How are antigens bound to Class II MHC?

A

Antigens taken up in intracellular vesicle

Early endosomes = endosomal proteases are inactive (neutral pH)

Acidification of vesicles activates proteases = degrade antigen into peptide fragments

Vesicle with peptides fuse with vesicles containing Class II MHC molecules

51
Q

How does Class II MHC antigen presentation occur?

A

Invariant chain forms a complex Class II molecules = blocks binding of peptides and misfolded proteins

Invariant chain is cleaved in an acidified endosome = leaving short peptide fragment (CLIP)

Endocytosed antigens are degraded to peptides in endosomes = CLIP still blocks binding

HLA-DM binds to Class II MHC = releasing CLIP

Class II MHC then travels to cell surface

52
Q
A