lecture 2- TCR, antigen recognition

Question 1

alpha-beta T cells may express either ___ or ___ which dictates their function as killers or helpers

Answer 1

CD4 or CD8

Question 2

CD8 binds ___ on MHC Class ___

Answer 2

alpha 3
MHC class I

Question 3

CD4 binds ___ on MHC Class ___

Answer 3

beta2
MHC Class II

Question 4

T cell receptors are never ___ and do not undergo ___ or ___

Answer 4

secreted
isotype switching
affinity maturation

Question 5

the antigen binding site of the TCR is formed by the ___ regions of both alpha and beta chains

Answer 5

variable

Question 6

T cells react with antigens with a ___ affinity than B cell receptors

Answer 6

lower

Question 7

Which of the following chains in TCR have D gene segments

Answer 7

beta

Question 8

Where do T cells undergo gene rearrangement?

Answer 8

thymus

Question 9

Describe the order of rearrangement events on the TCR genes

Answer 9

• in first round or rearrangement, beta gamma, delta all attempt rearrangement
  o if beta is successful, go on to have alpha attempt rearrangement
  o if beta not successful, delta and gamma try to rearrange
• if beta is made, it is tested with a pre-TCR – surrogate chain called pTalpha, testing for structural integrity – if successful, alpha rearranges, if successful, alpha loops out the delta chain- shuts off potential to make delta rearrangement

Question 10

If alpha is successfully rearranged, which chain cannot be expressed?

Answer 10

delta

Question 11

Which TCR chain can attempt rearrangement the most times?

Answer 11

alpha

Question 12

How many attempts can be made at each beta chain?

Answer 12

can try twice on each beta chain locus (4 potential attempts to make a beta chain)

Question 13

What molecular complex is required for TCR signaling? How many chains does it have?

Answer 13

CD3 – (cluster of differentiation)
- has 6 chains, each has its own special function, without all of them, CD3 does not work

Question 14

Before rearrangement T cell-committed thymocytes express neither ___ nor ____, so its called ___. Only after the ____ has been successfully tested, do they up-regulate expression of _____

Answer 14

CD4 CD8
double negative
pre-TCR (beta chain)
CD4 or CD8

Question 15

Alpha/betta are ___, meaning only the alpha/beta T cells that recognize ___ leave to enter periphery

Answer 15

MHC restrictive
MHC

Question 16

site of receptor rearrangement in B cells

Answer 16

bone marrow

Question 17

the pre-TCR is made up of ___

Answer 17

beta and pTalpha (surrogate alpha)

Question 18

chain with most attempts at rearrangement in B cells

Answer 18

kappa in light

Question 19

mechanism of antigen recognition in T cells

Answer 19

MHC + peptide

Question 20

name of signaling complex in T cells

Answer 20

CD3

Question 21

can receptor be refined after activation in B/T cells

Answer 21

T: no
B: yes

Question 22

Receptor can have different isotypes after activation in B/T cells

Answer 22

T: no
B: yes

Question 23

does BCR or TCR have the greatest potential diversity upon rearrangement?

Answer 23

TCR

Question 24

describe overview of TCR structure, function, and where they undergo processes

Answer 24

• always membrane-bound
• develop/rearrange/neg and pos selection in thymus
• TCR has 2 chains
• do not undergo isotype switching or affinity maturation
• TCR recognizes MHC-peptide
• T cells kill cells or make cytokines to clear infection

Question 25

where do B cells undergo positive selection

Answer 25

secondary lymphoid organs

Question 26

TCR has ___ chains rather than heavy/light chains

Answer 26

alpha/beta

Question 27

beta chain has ___ segments like heavy chain of BCR; alpha chain has a lot of ___ segments

Answer 27

D J

Question 28

like B cells, T cells generate receptors through ____

Answer 28

somatic recombination

Question 29

compare alpha/beta and gamma/delta

Answer 29

alpha/beta: majority of conventional T cells - recognize MHC/peptide - high degree of receptor diversity - cells abundant in all secondary lymphoid tissues gamma/delta: small subset of T cells - recognition specificity not clear, MHC Class Ib - lower degree of receptor diversity - cells abundant in gut mucosa

Question 30

upon activation, CD4+ helper T cells.... upon activation, CD8+ cytolytic T cells....

Answer 30

CD4+ produce cytokines to help other cells clear infection CD8+ kill target cells through various mechanisms (express perforin and granzymes- kill functions shared with NK cells

Question 31

antigens presented to CD4+ and CD8+ T cells tend to be from ____ and ___

Answer 31

extracellular sources cytoplasmic sources

Question 32

TCR needs signaling adaptor molecules called ___, have __ chains, needed for ___

Answer 32

CD3 6 expression on cell surface

Question 33

in TCR, there are regions of binding site that recognize ___ and other regions that recognize ___

Answer 33

MHC peptide

Question 34

describe steps in TCR formation

Answer 34

1- beta, gamma, and delta chains attempt rearrangement simultaneously -- in beta: V + J, then D + VJ . if beta is successful FIRST, then tested with pre-TCR (beta + pTalpha) . if gamma and delta are successful first, then rearrangement complete and cell will be gamma/delta 2- alpha, gamma, and delta chain attempt at same time . if alpha successful, combined with beta and pos and neg selection begins . if 2nd round of gamma and delta are successful, cells will be gamma/delta

Question 35

describe development of TCR starting with uncommitted progenitor

Answer 35

start with uncommitted progenitor in thymus that expresses CD34 --> committed double negative T cell progenitor (CD2), ready for rearrangement --> beta, gamma, delta rearrange --> if beta successful, pre-TCR testing (double positive- upregulates CD4 and CD8) --> alpha, gamma, delta rearrangements

Question 36

how many chances do gamma/delta have to be a gamma/delta cell

Answer 36

2

Question 37

gamma/delta do not go through this stage

Answer 37

do not express a pre-TCR because they are expressed at same time ( no time to test one or the other)

Question 38

testing the ability of a beta chain to form a complex with pTalpha chain stops ____

Answer 38

rearrangement at other beta locus- ALLELIC EXCLUSION

Question 39

how are alpha and delta chains intertwined?

Answer 39

the delta segments are located within the alpha locus, so rearrangement of alpha chain results in deletion of delta

Question 40

3 brief steps of alpha/beta rearrangement

Answer 40

1- D + J on beta 2- V + DJ on beta 3- V + J on alpha

Question 41

RAG1 and RAG2 are expressed when?

Answer 41

during rearrangement of beta and alpha chains