Antigen recognition: T cells and MHC Flashcards

1
Q

What are the equivalent of antibodies on T cells?

A

T cell receptors

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2
Q

How are T cells different from B cells?

A

T cells carry different receptors

T cells are encoded by different loci

B cells evolved after T cells

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3
Q

What evidence is there that B cells are more evolved that T cells?

A

T cells are found in simpler animals

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4
Q

How are the T cell receptors structurally different from B cell receptors?

A

TCR is made up of alpha and beta chains

BCR are made of a dimer of dimers

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5
Q

What is referred to when we say T cell receptors?

A

Receptors that specifically recognise antibodies

NOT the receptors for different cytokines and antibodies

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6
Q

How are BCR and TCR fundamentally different?

A

TCR are solely transmembrane

BCR can be secreted

TCRs are heterodimers, BCRs are dimers of dimers

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7
Q

Which mechanism of diversity exists in BCR but not TCR generation?

A

Somatic hypermutation

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8
Q

Which mechanisms of cell diversity are similar to B cells?

A

Multiple germline genes

V-J and V-D-J recombination

Recombinational inaccuracies

N-nucleotide addition

Chain combination

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9
Q

Describe the evolution of TCRs and BCRs

A

T and B cells are homologous

This is made obvious by their similarities

They are derived from one common ancestral gene that later evolved separately

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10
Q

How many times has the locus producing the T cell receptors evolved?

A

At least 3 times

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11
Q

What are the two types of TCRs found on T cells?

A

TCR ab

TCR gd

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12
Q

How are the two types of TCR different?

A

TCR ab is very common, occupying 50% of circulating lymphocytes

TCR gd is expressed by a distinct population of T cells with less variability than ab T cells, since there are less genes coding for them

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13
Q

What is the difference between the ways BCR and TCR recognise antigens?

A

BCR complementarity depends on the shape of the antigen

TCR complementarity does not depend on 3D shape, but rather recognises sequences of the antigen

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14
Q

Why is the way TCRs recognise antigens more efficient?

A

The shape of an antigen changes very readily as it evolves, so a recognition system based on this is not very efficient

T cells recognises smaller pieces of the pathogen which are difficult to change

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15
Q

What are MHCs?

A

Major Histocompatibility Complexes

Molecules which act to bind to the highly unstable peptides which T cell receptors recognise

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16
Q

What is another name for MHCs?

A

HLA

MHCs in humans

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17
Q

What is the shape of MHCs?

A

Single alpha chain composes the whole structure

Beta-2 microglobulin holds the structure together

Contain grooves where the antigen fits into

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18
Q

What is the shape of the groove antigens fit onto the MHC through?

A

Two a-helices

A b-pleated sheet floor

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19
Q

What happens when the peptides bind to the MHC?

A

Peptide becomes deeply embedded

Becomes an intrinsic part of the structure

Without it, the MHC is unstable

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20
Q

What do T cell receptors recognise?

A

T cells can only detect the amino acids exposed through the MHC

This hospot (antigen + MHC) is detected as non-self

So the TCR recognises the composite structure formed by the mixture of self (MHC) and non-self (viral/bacterial peptide)

21
Q

What type of binding occurs between the MHC hotspot and the TCR?

A

Covalent bond

Must be tightly controlled in order to retain the characteristic weak binding that remains a feature of T cells

This allows T cells to leave once bound to its target

22
Q

How specific must the MHC binding groove be?

A

The specificity must be tightly controlled

If it is too specific, no peptide would bind to it

If it is too broad, no peptide would bind strongly enough

23
Q

One MHC binds to one peptide

TRUE or FALSE

A

FALSE

One MHC binds to a lot of different peptides

MHC have pockets which only take amino acids which fit in specific positions

Investigations have shown the peptides that fit to a specific MHC have some similarities between them

24
Q

What type of interaction occurs between the MHC and the peptide?

A

Non-covalent

25
Q

What type of interaction occurs between the MHC hotspot and the T cell?

A

Covalent

26
Q

Which chromosome codes for MHC?

A

Chromosome 6

27
Q

What are the two types of MHC?

A

MHC I

MHC II

28
Q

How many genes code for MHC I? What are they called?

A

3 genes

A, B and C

29
Q

Which cells carry MHC I on their surface?

A

All nucleated cells

Therefore, at any rate, the T cell can recognise the infection of any cell of the body

30
Q

Examples of classical genes that code for HLA I

A

DPB2

DPA1

31
Q

How many different molecules form part of class II MHC?

A

3

Divided into DP, DQ and DR

32
Q

How is MHC variability increased?

A

Number of variants in each gene that code for HLA molecules

Each individuals inherits 2 HLA molecules which are codominantly expressed on each cell

Different subtypes of each HLA

33
Q

Which T cells recognise MHC II?

A

CD4 T cells

34
Q

Which T cells recognise MHC I?

A

CD8 T cells

35
Q

What is exogenous processing?

A

The process by which APCs present antigens on the MHC II following phagocytosis

36
Q

Describe the process of exogenous processing

A

The MHC II is made in the golgi

It is transported through vesicles and transformed in the process through the addition of sugars

MHC II meets the peptides are found in the loading compartment (endosomes)

Within the endosomes, proteins are cleaved and bound to the MHC

Then it becomes presented on the surface of APCs

37
Q

What is the target of CD4 T cells?

A

MHC II presenting peptides

On APCs

38
Q

What is endogenous processing?

A

Process of presenting peptides made intracellularly

Onto MHC I

39
Q

Describe the process of MHC I exogenous processing

A

MHC I are produced in the endoplasmic reticulum

A protein becomes degraded by the proteasome, and enters the endoplasmic reticulum through TAP proteins

The intracellular proteins bind to MHC inside the endoplasmic reticulum

The MHC I-antigen complex travels to the cell surface through the Trans-Golgi vesicle

40
Q

What are the two main differences between exogenous and endogenous processing?

A

Loading compartment

  • MHC II = endosome
  • MHC I = endopasmic reticulum

Peptide origin

  • MHC II = exogenous
  • MHC I = endogenous
41
Q

What does the MHC I bind to?

A

The peptides the MHC recognises are produced by the same cell making the MHC

42
Q

What is the purpose of the T cell receptor?

A

Signalling the cell to divide and differentiate to provide memory and effector function

43
Q

Can TCRs function on their own?

A

No

They need accessory molecules

CD3

These transduce the signal in the cell and cause differentiation upon binding of the antigen to the TCR

44
Q

Without costimulatory molecules, binding of the TCR would result in no response

TRUE or FALSE

A

TRUE

This specific interaction is necessary but not sufficient

45
Q

Which other costimulatory molecules are important for correct T cell functioning?

A

CD28

CTLA4

LFA1

46
Q

What do the costimulatory molecules CD28 and CTLA4 bind to?

A

CD80/86 on APCS

47
Q

What is the importance behind CTLA4/CD28 binding to CD80/86

A

Binding determines whether there is a response or not

Makes sure the response only occurs when needed

48
Q

What does LFA1 on T cells bind to?

A

ICAM on APCs

49
Q

What is the importance behind the LFA1/ICAM bond?

A

Ensured the cells bind long enough