lecture 2- TCR, antigen recognition Flashcards
alpha-beta T cells may express either ___ or ___ which dictates their function as killers or helpers
CD4 or CD8
CD8 binds ___ on MHC Class ___
alpha 3
MHC class I
CD4 binds ___ on MHC Class ___
beta2
MHC Class II
T cell receptors are never ___ and do not undergo ___ or ___
secreted
isotype switching
affinity maturation
the antigen binding site of the TCR is formed by the ___ regions of both alpha and beta chains
variable
T cells react with antigens with a ___ affinity than B cell receptors
lower
Which of the following chains in TCR have D gene segments
beta
Where do T cells undergo gene rearrangement?
thymus
Describe the order of rearrangement events on the TCR genes
- 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
If alpha is successfully rearranged, which chain cannot be expressed?
delta
Which TCR chain can attempt rearrangement the most times?
alpha
How many attempts can be made at each beta chain?
can try twice on each beta chain locus (4 potential attempts to make a beta chain)
What molecular complex is required for TCR signaling? How many chains does it have?
CD3 – (cluster of differentiation)
- has 6 chains, each has its own special function, without all of them, CD3 does not work
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 _____
CD4 CD8
double negative
pre-TCR (beta chain)
CD4 or CD8
Alpha/betta are ___, meaning only the alpha/beta T cells that recognize ___ leave to enter periphery
MHC restrictive
MHC
site of receptor rearrangement in B cells
bone marrow
the pre-TCR is made up of ___
beta and pTalpha (surrogate alpha)
chain with most attempts at rearrangement in B cells
kappa in light
mechanism of antigen recognition in T cells
MHC + peptide
name of signaling complex in T cells
CD3
can receptor be refined after activation in B/T cells
T: no
B: yes
Receptor can have different isotypes after activation in B/T cells
T: no
B: yes
does BCR or TCR have the greatest potential diversity upon rearrangement?
TCR
describe overview of TCR structure, function, and where they undergo processes
- 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
where do B cells undergo positive selection
secondary lymphoid organs
TCR has ___ chains rather than heavy/light chains
alpha/beta
beta chain has ___ segments like heavy chain of BCR; alpha chain has a lot of ___ segments
D
J
like B cells, T cells generate receptors through ____
somatic recombination
compare alpha/beta and gamma/delta
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
upon activation, CD4+ helper T cells….
upon activation, CD8+ cytolytic T cells….
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
antigens presented to CD4+ and CD8+ T cells tend to be from ____ and ___
extracellular sources
cytoplasmic sources
TCR needs signaling adaptor molecules called ___, have __ chains, needed for ___
CD3
6
expression on cell surface
in TCR, there are regions of binding site that recognize ___ and other regions that recognize ___
MHC
peptide
describe steps in TCR formation
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
describe development of TCR starting with uncommitted progenitor
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
how many chances do gamma/delta have to be a gamma/delta cell
2
gamma/delta do not go through this stage
do not express a pre-TCR because they are expressed at same time ( no time to test one or the other)
testing the ability of a beta chain to form a complex with pTalpha chain stops ____
rearrangement at other beta locus- ALLELIC EXCLUSION
how are alpha and delta chains intertwined?
the delta segments are located within the alpha locus, so rearrangement of alpha chain results in deletion of delta
3 brief steps of alpha/beta rearrangement
1- D + J on beta
2- V + DJ on beta
3- V + J on alpha
RAG1 and RAG2 are expressed when?
during rearrangement of beta and alpha chains
