T Cell Receptor

Question 1

Structure of T cell antigen receptor

Answer 1

• has a alpha chain and a beta chain
• there are carbohydrates attached
• there is a variable region on top and a constant region close to the T cell
• the hinge is between the constant region on the transmemebrane region and there is a disulfide bond there
• there is a cytoplasmic tail in the cytoplasm of the T cell

Question 2

T cell and B cell recognition of antigen

Answer 2

• B cells can recognize linear or conformational epitopes in proteins, carbohydrates, or lipids. A membrane form of ig is responsible for antigen recognition
• T cells, recognize linear peptide fragments bound to MHC class I or class I molecules

Question 3

Biochemical characterization of the TCR

Answer 3

• disulfide linked heterodimer
• transmembrane protein
• constant and variable regions
• both chains are glycoproteins

Question 4

Generating a Diverse TCR Repertoire

Answer 4

• recombination of different gene segments (V, D and J segments)
• recombination of different numbers of gene segments (TCR delta locus)
• imprecise joining of gene segments
• P and N nucleotide addition TdT
• assembly of different combinations or rearraged TCR chains (alpha + beta, gamma + delta)

however, unlike immunoglobulin genes, somatic mutation of TCR genes does not take place

Question 5

Diversity in antibodies and TCR

Answer 5

-total potential diversity in Ig- ~10^11
in TCR alphabeta ~10^16
-in TCR gammadelta ~10^18

Question 6

T cells monitor the intracellular environment of the host cell

Answer 6

• Cytosolic pathogens: degraded in cytosol; peptides bind to MHC I; presented to Cd8 T cells; effect on presenting cell-death
• Intravesicular pathogens: degraded in endocytic vesicles; peptides bind to MHC class II; present in CD4 T cells; on presenting cell activates to kill intravesicular bacteria and parasites
• Extracellular pathogens and toxins: degraded in endocytic vesicles; MHC II; CD4 T cells; activation of B cells to secrete Ig to eliminate extracellular bacteria/ toxins

Question 7

TCR recognition of MHC complex

Answer 7

• simultaneous recognition of MHC specificity and peptide specificity
• TCR affinity for peptide and MHC is very weak relative to antibodies
• Kd for TCRalphabeta- 10^-5 - 10^-7M
• Kd for Ig- 10^-7 to 10^-11 M

Question 8

CD4 and CD8

Answer 8

• function as co-receptors on T cells, increasing TCR sensitivity for peptide-MHC
• CD4- D1, D2, D3, D4
• CD8- alpha and beta parts
• CD4 and CD8 interact with non-variable regions of MHC II and MHC I respectively

Question 9

Superantigens

Answer 9

• bacterial enterotoxins- staphylococcal, Streptococcal and Mycobacterial
• Minor Lymphocyte stimulating MIs antigens- Endogenous mouse retroviral products
• unidenified endogenous antigens

Question 10

Diseases caused for superantigens

Answer 10

• Staphylococcal enterotoxins- S. aureaus- Food poisoning, shock
• Toxic shock syndrome toxin- S. aureus
• exfollating toxins A and B- S. aureus Scalded Skin syndrome
• Pyrogenic exotoxins A B C- S pyogenes- fever rash shock
• M. arthritides mitogen- shock

Question 11

SEB/ TCR/ MHC

Answer 11

• structual model
• the SEB binds to part of the MHC and TCR and causes non-specific binding
• you get a huge reaction
• 1/4 responsive T cells instead of 1 in 10^4

Question 12

Gene structure of human MHC/HLA

Answer 12

• there are class I HLAs- A B and C
• there are class II HLAs that come first on the gene- DP, DQ, DR
• the DM and DO don’t present, they help load
• human MHC genes are highly polymorphic
• have to recognize both the MHC and the peptide

Question 13

Differential tissue expression of MHC molecules

Answer 13

• MHC I are expressed on all nucleated cells
• MHC II are expressed on subset of hematopoietic cells ad thymic stromal cells- T cells, B cells, macrophages, Langerhands cells, epithelial cells of thymus

Question 14

Structure of MHC I

Answer 14

• monomer
• has a peptide binding cleft between alpha 2 and 1 subunits
• alpha 3 subunit goes into cytoplasma
• and then there is B2 microglobulin which is non-variable
• can hold about 9 aa

Question 15

Structure of MHC II

Answer 15

• has peptide binding cleft between alpha 1 and beta 1
• alpha 2 and beta 2 go into the cytoplasm
• there is a disulfide bond
• can hold 15-16 aa

Question 16

MHC II antigen processing pathway

Answer 16

• antigen is taken up into intracellular vesicles
• in early endosomes of neutral pH endosomal proteases are inactive
• acidication of vesicles activates proteases to degrade antigen into peptide fragments
• vesicles containing peptides fuse with vesicles containing MHC II molecules

Question 17

MHC I antigen processing pathway

Answer 17

• protein
• proteasome
• TPP II
• amino-peptidase
• TAP
• ERAAP
• up to the cell surface already loaded on MHC
• a lot of the time the MHC have pieces of our own proteins in them