Lecture 9 - MHC Flashcards Preview

MIIM30002 - Principles of Immunology > Lecture 9 - MHC > Flashcards

Flashcards in Lecture 9 - MHC Deck (46):
1

Why do we need T cells?

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

2

What are the two types of T cell?

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

'Helper' T cells:
• help B cells & macrophages
• CD4+

3

What are the CD molecules?

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

4

What does MHC stand for?

Major histocompatibility complex

5

How are T cells 'activated'?

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

6

What sort of epitopes can TCR's bind?

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

7

What are the regions on the MHC I molecule?

• Peptide binding region
• Ig like region
• Transmembrane region
• Cytoplasmic region

• α1
• α2
• α3
• β2

8

What are the regions on the MHC II molecule?

• Peptide binding region
• Ig like region
• Transmembrane region
• Cytoplasmic region

• α1
• α2
• β1
• β2

9

Which accessory molecules do CTL and Th cells have?

CTL: CD8
Th cells: CD4

10

Describe the specificity of TCR's

Specific for:
• peptide
• MHC

11

On which cells are the various MHC molecules expressed?

MHC I: all nucleated cells

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

Expression upregulated:
• during immune response

12

What is the genetic locus that encodes MHC in humans?
And in mice?

HLA locus
• Human Leukocyte Antigens

Mice:
H-2 locus

13

Describe the structure of the MHC locus
Draw this

• Locus contains regions
• Regions contain genes
S25

14

Which genes code for MHC I in humans?

B
C
A

15

Which genes code for MHC II in humans?

DP
DQ
DR

16

Which genes code for MHC I in mice?

K
D

17

Which genes code for MHC II in mice?

I:
• I-A
• I-E

18

What is the difference between 'polymorphism' and 'allele'

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

19

What is the notation for the various HLA alleles?

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

20

What is a haplotype?
Compare this to genotype

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

What can be said about the haplotype of inbred mice?

Will be the same as the genotype

22

What is the heavy and light chain of MHC I?

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

23

How many extracellular domains on MHC I?
How about MHC II?

4 extracellular domains in each

24

Describe the peptide binding cleft in MHC II

α1 & β1

25

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

Not covalently bound

26

What are TCRs specific for?

Specific for:
• peptide
• MHC

27

Where does the peptide antigen bind to MHC?

Peptide binding groove

28

Describe the pattern of expression of HLA genes

Co-dominant
• both alleles expressed simultaneously

29

What is the nomenclature for mouse MHC alleles?

Letter superscripts
eg.
H-2 K^b

30

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

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

31

Are MHC genes polymorphic?
What does this affect?

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

This affects:
• peptide binding cleft
• TCR binding

32

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

Infected cell is expressing molecules on their cell surface

33

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

Not covalently bonded

34

Describe the peptide binding cleft in MHC I

α1 & α2

35

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

Not covalently bound

36

What is important about CD4?

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

37

What is important about CD8?

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

38

Where is β2-microglobulin encoded?

Chromosome 15

39

What is the nomenclature for mouse MHC alleles?

Letter superscripts
eg.
H-2 K^b

40

What is meant by: 'MHC molecules are restricted'?

They are highly specific for certain TCR and peptides

41

Which MHC do TCR's recognise?

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

42

On which chromosome are the HLA genes?

HLA class I and II: Chromosome 6

β2m: Chromosome 15

43

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

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

Describe the changes to MHC expression during an immune response

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

45

The binding pockets of MHC molecules is altered by...

Polymorphism

46

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?

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