Lecture 9 - MHC Flashcards

1
Q

Why do we need T cells?

A

CTL: once viruses get into cells, we need a way of detecting this and killing off the cells
Ab’s are only good for blocking them before they gain access

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2
Q

What are the two types of T cell?

A

Cytotoxic T cell:
• killing of infected / transformed cells
• CD8+

‘Helper’ T cells:
• help B cells & macrophages
• CD4+

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3
Q

What are the CD molecules?

A

“Cluster of differentiation”
• Found on only subsets of leukocytes
• Classify the cell and/or stage of differentiation

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4
Q

What does MHC stand for?

A

Major histocompatibility complex

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5
Q

How are T cells ‘activated’?

A

Angtigen presented to their TCR’s by APC’s using MHC’s
CTL: MHC I
T helper cells: MHC II

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6
Q

What sort of epitopes can TCR’s bind?

A

Only short, linear epitopes
• 8-11 aa long
Must be present by an APC

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7
Q

What are the regions on the MHC I molecule?

A
  • Peptide binding region
  • Ig like region
  • Transmembrane region
  • Cytoplasmic region
  • α1
  • α2
  • α3
  • β2
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8
Q

What are the regions on the MHC II molecule?

A
  • Peptide binding region
    • Ig like region
    • Transmembrane region
    • Cytoplasmic region
  • α1
  • α2
  • β1
  • β2
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9
Q

Which accessory molecules do CTL and Th cells have?

A

CTL: CD8

Th cells: CD4

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10
Q

Describe the specificity of TCR’s

A

Specific for:
• peptide
• MHC

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11
Q

On which cells are the various MHC molecules expressed?

A

MHC I: all nucleated cells

MHC II: antigen presenting cells:
 • mϕ
 • DC's
 • B cells
 • Langerhan's cells

Expression upregulated:
• during immune response

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12
Q

What is the genetic locus that encodes MHC in humans?

And in mice?

A

HLA locus
• Human Leukocyte Antigens

Mice:
H-2 locus

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13
Q

Describe the structure of the MHC locus

Draw this

A

• Locus contains regions
• Regions contain genes
S25

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14
Q

Which genes code for MHC I in humans?

A

B
C
A

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15
Q

Which genes code for MHC II in humans?

A

DP
DQ
DR

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16
Q

Which genes code for MHC I in mice?

A

K

D

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17
Q

Which genes code for MHC II in mice?

A

I:
• I-A
• I-E

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18
Q

What is the difference between ‘polymorphism’ and ‘allele’

A

Allele: version of a gene
Polymorphism: existence of different alleles

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19
Q

What is the notation for the various HLA alleles?

A

Numbered system: each allele has different number
e.g.
• HLA-A2
• HLA-DR5

20
Q

What is a haplotype?

Compare this to genotype

A

Haplotype: Grouping of different alleles found on a given chromosome (i.e., just one of the chromosomes)

Genotype: alleles present within an individual, i.e. alleles on both chromosomes

21
Q

What can be said about the haplotype of inbred mice?

A

Will be the same as the genotype

22
Q

What is the heavy and light chain of MHC I?

A

Heavy: α1, α2 & α3
Light: β2-microglobulin

23
Q

How many extracellular domains on MHC I?

How about MHC II?

A

4 extracellular domains in each

24
Q

Describe the peptide binding cleft in MHC II

A

α1 & β1

25
Q

Describe the association between the alpha and beta chain of MHC II

A

Not covalently bound

26
Q

What are TCRs specific for?

A

Specific for:
• peptide
• MHC

27
Q

Where does the peptide antigen bind to MHC?

A

Peptide binding groove

28
Q

Describe the pattern of expression of HLA genes

A

Co-dominant

• both alleles expressed simultaneously

29
Q

What is the nomenclature for mouse MHC alleles?

A

Letter superscripts
eg.
H-2 K^b

30
Q

In humans, which is more complex: haplotype or genotype?

A

Genotype is more complicated, because it concerns genes on both chromosomes

31
Q

Are MHC genes polymorphic?

What does this affect?

A

Yes, very much so.
There are as many as 100 different alleles for some HLA genes

This affects:
• peptide binding cleft
• TCR binding

32
Q

How can CTL’s recognise infected cells (in general)?

A

Infected cell is expressing molecules on their cell surface

33
Q

How are the heavy and light chains associated in MHC I?

A

Not covalently bonded

34
Q

Describe the peptide binding cleft in MHC I

A

α1 & α2

35
Q

Describe the association between the alpha and beta chain of MHC II

A

Not covalently bound

36
Q

What is important about CD4?

A
  • Found on Th cells
  • Recognises the MHC II molecule
  • binds to β2 domain
37
Q

What is important about CD8?

A
  • Found on CTL
  • Recognises MHC I molecule
  • binds to α2 domain
38
Q

Where is β2-microglobulin encoded?

A

Chromosome 15

39
Q

What is the nomenclature for mouse MHC alleles?

A

Letter superscripts
eg.
H-2 K^b

40
Q

What is meant by: ‘MHC molecules are restricted’?

A

They are highly specific for certain TCR and peptides

41
Q

Which MHC do TCR’s recognise?

A

A given T cell will only recognise ONE of the MHC molecules in an individual

42
Q

On which chromosome are the HLA genes?

A

HLA class I and II: Chromosome 6

β2m: Chromosome 15

43
Q
Where are the disulphide bonds in the following:
 • MHC class I
 • MHC class II
A

MHC I:
• Within all domains (α1, α2, α3 and β2m)
• NB there are no disulphide bonds between the α and β chains

MHC II:
• No disulphide bonds between either the chains or within domains

44
Q

Describe the changes to MHC expression during an immune response

A

MHC class I & MHC class II expression upregulated during an immune response

45
Q

The binding pockets of MHC molecules is altered by…

A

Polymorphism

46
Q

If one only has a maximum of 6 versions of both MHC class I & II, how can all the different epitopes be presented on these molecules?

A

Epitopes have anchor residues that are conserved

These common anchor residues bind into the binding pockets of the peptide binding cleft of the MHC molecule