Linking Innate and Adaptive Immunity 3

Question 1

what do TCRs recognize? where?

Answer 1

peptide-MHC complexes on the surface of APCs

Question 2

what is an immunological synapse?

Answer 2

T cell:APC contact, with the TCR complex

Question 3

what are the 4 components of the TCR complex? describe each component’s location in the complex

Answer 3

1. TCR –> in the middle
2. CD3 –> 1 on either side of TCR
3. zeta chain –> 2 inside cell
4. ITAM –> on intracellular part of CD3 and zeta chains

Question 4

what is ITAM?

Answer 4

Immunoreceptor Tyrosine-based Activation Motif

Question 5

what does the TCR complex trigger?

Answer 5

intracellular signaling

Question 6

what type of molecule is TCR?

Answer 6

HETERODIMER

Question 7

what type of proteins are involved in TCR?

Answer 7

transmembrane proteins

Question 8

is TCR secreted?

Answer 8

no, it is membrane-bound

Question 9

what are the 2 main types of TCR? which is most common?

Answer 9

1. alpha-beta TCR (most common)
2. gamma-delta TCR (<10%)

Question 10

what are the 2 types of chains on the most common TCR?

Answer 10

1. ALPHA
2. BETA

Question 11

what does clonotypic mean?

Answer 11

the cells of a given clone all have identical receptors

Question 12

what are the 2 main subunits of each chain?

Answer 12

1. Variable (V)
2. Constant (C)

Question 13

how many TCR and BCR are possible? why?

Answer 13

billions! to allow for increased specificity

Question 14

how does the number of adaptive immune receptors compare to the number of innate immune receptors? why?

Answer 14

there are <100 innate immune receptors (PRRs) because they don’t need to be very specific

Question 15

BCR and TCR genes undergo __________

Answer 15

BCR and TCR genes undergo DNA rearrangement

Question 16

what are the 4 gene segments of BCR and TCRs?

Answer 16

1. Variable (V)
2. Diversity (D)
3. Joining (J)
4. Constant (C)

Question 17

what are gene segments?

Answer 17

short DNA sequences

Question 18

what domains are in the alpha chain?

Answer 18

V, J, C

Question 19

what domains are in the beta chain?

Answer 19

V, D, J, C

Question 20

where does TCR rearrangement occur?

Answer 20

in the thymus

Question 21

what is another term for gene rearrangement?

Answer 21

somatic recombination

Question 22

what is somatic recombination/gene rearrangement?

Answer 22

recombination of gene segments in TCR genetic loci to make a functional gene

Question 23

describe gene rearrangement for alpha chain

Answer 23

1 V, J, and C are selected in the DNA to be transcribed and translated into an alpha chain

Question 24

describe gene rearrangement for beta chain

Answer 24

1 V, D, J, and C are selected in the DNA to be transcribed and translated into a beta chain

Question 25

how many variations of TCRs are possible? how is this variability achieved?

Answer 25

billions of variations possible many combos of each subunit are possible, and many combos of alpha and beta chains are possible

Question 26

why don't TCRs recognize the peptide by itself?

Answer 26

TCRs only recognize the peptide when MHC is present --> TCR interacts with both peptide and MHC

Question 27

what are the 2 types of APCs?

Answer 27

1. Professional APC 2. Non-professional APC

Question 28

what 3 types of cells are professional APC?

Answer 28

1. DCs 2. macrophages 3. activated B cells

Question 29

what type of cells are non-professional APC?

Answer 29

all nucleated cells in the body

Question 30

what type of MHCs do professional APC express?

Answer 30

1. MHC Class I 2. MHC Class II

Question 31

what do professional APCs express when activated?

Answer 31

express costimulatory molecules when activated

Question 32

what type of MHCs do non-professional APC express?

Answer 32

MHC Class I only

Question 33

when do non-professional APC express MHC Class I?

Answer 33

under normal conditions to show that they are healthy

Question 34

do non-professional APC express costimulatory molecules?

Answer 34

no

Question 35

what do MHC Class I molecules bind and present?

Answer 35

bind and present peptides generated within the cell --> endogenous proteins, self proteins

Question 36

what do MHC Class II molecules bind and present?

Answer 36

bind and present peptides of extracellular origin --> exogenous peptides

Question 37

what type of cells do MHC Class I molecules activate?

Answer 37

CD8+ T cells

Question 38

what do CD8+ T cells become when they become effector cells?

Answer 38

cytotoxic T cells

Question 39

what type of cells do MHC Class II molecules activate?

Answer 39

CD4+ T cells

Question 40

what do CD4+ T cells become when they become effector cells?

Answer 40

T helper cells

Question 41

what subunits are in the MHC Class I molecule?

Answer 41

- 1 transmembrane alpha protein - 1 beta-microglobulin protein - 2 alpha proteins that make up the peptide-binding cleft

Question 42

what subunits are in the MHC Class II molecule?

Answer 42

- 1 beta, 1 alpha transmembrane proteins - 1 beta, 1 alpha proteins that make up the peptide-binding cleft

Question 43

what subunit of MHC Class I molecule is present in every MHC Class I molecule?

Answer 43

beta-microglobulin

Question 44

what are the 3 components of the MHC Class I molecule that is required to be stably expressed on the cell surface?

Answer 44

1. peptide 2. MHC Class I alpha chain (for 3 subunits) 3. beta-microglobulin

Question 45

what are the 3 components of the MHC Class II molecule that is required to be stably expressed on the cell surface?

Answer 45

1. peptide 2. MHC Class II alpha chains 3. MHC Class II beta chains

Question 46

each chain of the MHC has several _____________ domains

Answer 46

each chain of the MHC has several IMMUNOGLOBULIN-LIKE domains

Question 47

what are immunoglobulin-like domains?

Answer 47

secondary structure in many immune molecules

Question 48

besides TCRs, where are immunoglobulin-like domains found?

Answer 48

adhesion molecules

Question 49

what are the 4 components of immunoglobulin-like domains?

Answer 49

1. ~100 amino acids 2. alpha helices 3. beta sheets 4. stabilized by disulfide bond

Question 50

where is the more conserved location of MHC located?

Answer 50

closer to cell membrane

Question 51

where are the most variable regions of MHC located?

Answer 51

mostly around peptide-binding cleft

Question 52

what is the shape of MHC?

Answer 52

MOOSE

Question 53

how is beta-microglobulin bound to the rest of MHC?

Answer 53

bound at transmembrane alpha domain by non-covalent bond

Question 54

what length of peptides do MHC Class I molecules bind?

Answer 54

short peptides --> 8-10 amino acids

Question 55

what length of peptides do MHC Class II molecules bind?

Answer 55

length doesn't matter

Question 56

what allows for a stable interaction between TCR and peptide-MHC?

Answer 56

co-receptors

Question 57

why are co-receptors required?

Answer 57

because TCR and peptide-MHC is a low affinity interaction

Question 58

which co-receptor is used for MHC Class I ?

Answer 58

CD8

Question 59

which co-receptor is used for MHC Class II?

Answer 59

CD4

Question 60

co-receptors physically interact with __________

Answer 60

co-receptors physically interact with MHC

Question 61

describe the structure of CD4

Answer 61

- single chain transmembrane protein - 4 Ig-like domains (all identical)

Question 62

describe the structure of CD8

Answer 62

- heterodimer linked by disulfide bond - each transmembrane chain has 1 Ig-like domain

Question 63

what are the 2 roles of CD4 and CD8 co-receptors?

Answer 63

1. bind MHC molecule and enhance affinity of TCR-pMHC interaction 2. initiation of intracellular signaling from TCR (signal 1)