Lecture 9 - MHC Flashcards by Eleanor Nicklason

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

How well did you know this?

Not at all

Perfectly

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+

How well did you know this?

Not at all

Perfectly

What are the CD molecules?

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

How well did you know this?

Not at all

Perfectly

What does MHC stand for?

Major histocompatibility complex

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What sort of epitopes can TCR’s bind?

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

How well did you know this?

Not at all

Perfectly

What are the regions on the MHC I molecule?

Peptide binding region
Ig like region
Transmembrane region
Cytoplasmic region
α1
α2
α3
β2

How well did you know this?

Not at all

Perfectly

What are the regions on the MHC II molecule?

Peptide binding region
- Ig like region
- Transmembrane region
- Cytoplasmic region
α1
α2
β1
β2

How well did you know this?

Not at all

Perfectly

Which accessory molecules do CTL and Th cells have?

CTL: CD8

Th cells: CD4

How well did you know this?

Not at all

Perfectly

Describe the specificity of TCR’s

Specific for:
• peptide
• MHC

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What is the genetic locus that encodes MHC in humans?

And in mice?

HLA locus
• Human Leukocyte Antigens

Mice:
H-2 locus

How well did you know this?

Not at all

Perfectly

Describe the structure of the MHC locus

Draw this

• Locus contains regions
• Regions contain genes
S25

How well did you know this?

Not at all

Perfectly

Which genes code for MHC I in humans?

B
C
A

How well did you know this?

Not at all

Perfectly

Which genes code for MHC II in humans?

DP
DQ
DR

How well did you know this?

Not at all

Perfectly

Which genes code for MHC I in mice?

How well did you know this?

Not at all

Perfectly

Which genes code for MHC II in mice?

I:
• I-A
• I-E

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

What is the notation for the various HLA alleles?

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

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

What can be said about the haplotype of inbred mice?

Will be the same as the genotype

What is the heavy and light chain of MHC I?

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

How many extracellular domains on MHC I?

How about MHC II?

4 extracellular domains in each

Describe the peptide binding cleft in MHC II

α1 & β1

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

Not covalently bound

What are TCRs specific for?

Specific for: • peptide • MHC

Where does the peptide antigen bind to MHC?

Peptide binding groove

Describe the pattern of expression of HLA genes

Co-dominant | • both alleles expressed simultaneously

What is the nomenclature for mouse MHC alleles?

Letter superscripts eg. H-2 K^b

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

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

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

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

Infected cell is expressing molecules on their cell surface

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

Not covalently bonded

Describe the peptide binding cleft in MHC I

α1 & α2

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

Not covalently bound

What is important about CD4?

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

What is important about CD8?

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

Where is β2-microglobulin encoded?

Chromosome 15

What is the nomenclature for mouse MHC alleles?

Letter superscripts eg. H-2 K^b

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

They are highly specific for certain TCR and peptides

Which MHC do TCR's recognise?

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

On which chromosome are the HLA genes?

HLA class I and II: Chromosome 6 β2m: Chromosome 15

``` 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

Describe the changes to MHC expression during an immune response

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

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

Polymorphism

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