Adaptive immunity 3

Question 1

describe the structure of a T cell receptor

Answer 1

2 polypeptide chains of the same size

no heavy or light chains
(Alpha chain resembles light, Beta resembles heavy)

variable, constant + transmembrane regions

all variation comes from the 3 variable loops in the 2 chains

always membrane bound

Question 2

what are CDRs?

Answer 2

complementary-determining regions

part of the variable chains
- where antigens bind

Question 3

what generates T-cell receptor diversity?

what does this process use?

Answer 3

gene rearrangement
- addition of P + N nucleotides

uses RAG1 + RAG2

Question 4

what are the loci of a and b chains?

Answer 4

a = chr14
b = chr7

Question 5

what rearrangement is required for a functional a chain TCR?

what about for a b chain locus?

Answer 5

need a V and J regions to recombine

need a VDJ recombination

Question 6

where is TCR diversity generated?

Answer 6

in the CDRs

= CDR1-3

Question 7

how to T cell loci recombine?

Answer 7

T-cell specific TFs open up chromatin at TCR loci

-> allows recombination

Question 8

TCRs are only expressed when…?

where are these proteins located?

Answer 8

when in a complex with other proteins (CD3 complex)

CD3 gamma, delta + epsilon closely i=linked on chr11

zeta chain encoded on chr1

Question 9

why is the TCR complex with CD3 necessary?

Answer 9

without CD3 complex,

cytoplasmic tails of TCR are too short to activate signal transduction when an antigen binds

Question 10

what is the alternative TCR form on some T cells?

Answer 10

gamma:delta receptor

Question 11

what form must antigens be in for TCRs to recognise them?

what form are these antigens in?

Answer 11

bound to MHC molecules

short peptides

Question 12

what are the 2 main classes of T cell?

what do they recognise?

Answer 12

CD4
= co-receptor required for T cell recognition of MHC II peptides

CD8
= co-receptor required for T cell recognition of MHC I peptides

Question 13

what are the functions of CD4 and CD8 positive T cells?

Answer 13

CD8 positive
= cytotoxic T cells

CD4 positive
= T helper cells
- can be divided further:
e.g. TH1 cells activate tissue macrophages to take up antigen

Question 14

what are the 2 classes of MHC molecules?

Answer 14

MHC I
- present peptides derived from intracellular antigens

MHC II

• present peptides derived from extracellular pathogens
• only on specific APCs e.g. macrophages or DCs

Question 15

what are MHC molecules?

Answer 15

membrane glycoprotein

bind to an antigen + present it to T-cells

class I and II have similar 3D structure but are formed in different ways

Question 16

what are the different domains within MHC I and MHC II molecules?

Answer 16

MHC I:
a1, a2, a3 + b2-microglobulin

MHC II:
a1, a2, b1 + b2

Question 17

how do CD4 and CD8 work?

Answer 17

they form contact with the MHC molecule + strengthen the interaction

they do not bind to the peptide being presented

Question 18

what limits the length of peptides that can bind to MHC molecules?

how long are MHC I peptides usually?

what determines whether or not a peptide will bind to an MHC I?

Answer 18

the length of the peptide-binding groove

9 amino acids long

the N and C-termini

Question 19

what length are MHC II peptides?

why are these longer?

Answer 19

13-25 amino acids

they aren’t pinned down in the peptide binding groove at their N and C-termini

Question 20

describe antigen processing and presentation by MHC I molecules

Answer 20

1. protein antigen (e.g. viral) enters cell
2. peptides are generates by proteasome in cytosol
3. peptides transported into ER lumen by TAP (transporter associated with antigen processing)
4. associates with MHC I
5. transported to cell surface

Question 21

what happens if proteins are not fully folded in the ER?

Answer 21

held in the ER by chaperones

e.g. alpha subunit half by calnexin until it associated with beta2-microglobulin

Question 22

what proteins do MHC1 molecules form a complex with before they can leave the ER?

what does this ensure?

Answer 22

calreticulin

tapasin

TAP

MHC I cannot leave the ER unless they have bound peptide

Question 23

how are MHC I exported from the ER to the cell surface?

Answer 23

via vesicles through the Golgi Apparatus

Question 24

describe MHC II presentation process

Answer 24

1. antigens then up by phagocytosis or endocytosis
2. degraded by proteases in lysosomes
3. loading of peptides onto MHCII via MHC class II compartment
4. gets transported to cell surface

Question 25

why don’t MHC II molecules bind to peptides in the ER?

so what is the process of peptide binding?

Answer 25

the a + b chains are associated with an invariant chain (prevents binding in ER)

• > this chain is degraded in vesicles
• > leaves CLIP fragment bound
• > CLIP blocks peptide binding to MHC II in vesicles
• > CLIP is removed by HLA-DM

= peptides can bind