TCR Recognition

Question 1

TCR structure - similarities with BCR structure

Answer 1

*composed of 2 types of polypeptides: the alpha and beta chains
*individual polypeptides of the TCR contain variable and constant regions
*antigen binding site at the N-terminus of both alpha and beta chains

Question 2

TCR structure - differences with BCR structures

Answer 2

*only ONE antigen-binding site
*NEVER SECRETED from the T cell
*only recognizes peptides complexed with self HLA
*no affinity maturation
*weak interactions with the antigen

Question 3

signal transmission in TCRs

Answer 3

-the transmembrane portion of the TCR is too short for effective signal transmission
*CD3 is a complex of several proteins that INTERACTS WITH THE TCR to allow signal transmission through ITAMs (a series of phosphorylation events)

Question 4

how do we generate TCR diversity

Answer 4

1. V/J rearrangement on the alpha chain and V/D/J rearrangement on the beta chain
2. junctional diversity (TdT adding random nucleotides at rearrangement joints)
3. combinatorial diversity: any alpha chain can associate with any beta chain

Question 5

does the T cell receptor undergo affinity maturation

Answer 5

NO… thus, the TCR-epitope interaction is generally weaker than the BCR-epitope interaction

Question 6

TCR-HLA interaction

Answer 6

1. local dendritic cells sample antigen and migrate to the nearest lymph node
2. dendritic cells present antigenic peptides on HLA to the T cells

Question 7

CD4+ T cells recognize peptide presented by?

Answer 7

HLA (MHC) Class II

Question 8

CD8+ T cells recognize peptide presented by?

Answer 8

HLA (MHC) Class I

Question 9

which cells express HLA Class I

Answer 9

every nucleated cell in the body (thus, every cell except RBCs)

Question 10

which cells express HLA Class II

Answer 10

only professional antigen-presenting cells (dendritic cells, B cells, macrophages)

Question 11

how long is the peptide on HLA Class I

Answer 11

8-10 amino acids (derived from intracellular sources)
*requires anchor residues

Question 12

how long is the peptide on HLA Class II

Answer 12

13-25 amino acids (typically derived from extracellular sources)
*requires anchor residues

Question 13

genetic characteristics of HLA molecules

Answer 13

*polygenic (the presence of several related genes with similar functions)
*polymorphic (relatively large number of alleles for each type of HLA gene, except HLA-DRalpha)
*co-dominantly expressed (express both mom’s and dad’s copy)

Question 14

three sets of genes for HLA class I

Answer 14

HLA-A
HLA-B
HLA-C

MHC I loci have 1 letter

Question 15

three sets of HLA Class II

Answer 15

HLA-DPalphabeta
HLA-DQalphabeta
HLA-DRalphabeta

MHC II loci have 2 letters

Question 16

structure of HLA Class I complex

Answer 16

-heterodimer
*LONG alpha chain (alpha-1, -2, and -3)
*SHORT beta2-MICROGLOBULIN

Question 17

beta2-microglobulin

Answer 17

*highly conserved; part of HLA class I
*stabilizes the alpha chain
*KEEPS HLA I ON THE CELL SURFACE

Question 18

structure of HLA Class II

Answer 18

-heterodimer
-alpha chain (alpha-1 and alpha-2)
-beta chain (beta-1 and beta-2)

Question 19

anchor residues

Answer 19

*required by ALL HLA complexes (class I and II)
*class I and class II have preference for different sets of anchor residues
*anchor residues are critical for the peptide-HLA interaction

Question 20

TCR recognition requires BOTH ?

Answer 20

correct HLA and correct peptide

Question 21

superantigens

Answer 21

simultaneously bind specific TCR Vbeta chain and specific HLA molecules, causing:
*cross-linking
*T cell activation
*massive cytokine release

Question 22

2 examples of superantigens you should know

Answer 22

1. Staph aureus
2. Strep pyogenes

Question 23

superantigen: staph aureus

Answer 23

causes toxic shock syndrome via TSST-1 toxin

Question 24

superantigen: strep pyogenes

Answer 24

causes toxic shock-like syndrome via erythrogenic exotoxin A

Question 25

bare lymphocyte syndrome

Answer 25

failure to express HLA class II on B cells
*tx = bone marrow transplant

Question 26

what kinds of pathogens are presented by HLA class I

Answer 26

*present endogenous antigens (eg. viral or cytosolic proteins) to CD8+ cytotoxic T cells
*INTRAcellular pathogens (such as viruses) are presented and activate CD8+ T cells
*activated T cells kill infected cells and secrete viral cytokines

Question 27

what kinds of pathogens are presented by HLA class II

Answer 27

*present EXOGENOUS antigens (bacterial proteins) to CD4+ helper T cells
*EXTRAcellular pathogens (such as bacteria) are presented and activate CD4+ T cells
*activated T cells help activate B cells, resulting in antibody production for pathogen clearance

Question 28

TAPs (transporter associated with antigen processing)

Answer 28

*crucial for antigen processing and presentation for HLA class I

Question 29

antigen processing and presentation: HLA class I

Answer 29

*after intracellular proteins from the cytosol are degraded by the proteosome, TAPs transport peptides to the ER, where they can get loaded onto HLA class I
*the peptide-class I complex then gets expressed on the surface of the cell

**REQUIRES TAPs

Question 30

Dm and Li (invariant chain)

Answer 30

*crucial for antigen processing and presentation for HLA class II

Question 31

antigen processing and presentation: HLA class II

Answer 31

*uptake of extracellular proteins into an endosome, which fuses with a lysosome, and the proteins are degraded
*meanwhile, Li (invariant chain) inserts a CLIP fragment into the HLA class II to maintain its stability
*once the HLA class II gets to the antigen, the Dm molecule releases the CLIP molecule so that the pathogen epitope can bind
*peptide-HLA class II complex can be expressed on the surface of the cell