T Cell Receptors

Question 1

T cell antigen receptor

Answer 1

• stucture
• genetic diversity
• assembly and surface expression
• nature of antigen and antigen recognition

Question 2

MHC

Answer 2

• described by function-histocompatibility-molecules associated with what happens when you reject and organ
• HLA is human- monitor
• present short peptides
• fragments are from pathogens- can be self, T cells only react to foreign

Question 3

pathogens are not

Answer 3

-visible intracellularly

Question 4

B cells recognize

Answer 4

• linear of conformational epitopes in proteins, carbohydrates, or lipids
• a membrane form of Ig is responsible for antigen recognition

Question 5

T cells recognize

Answer 5

-linear peptide fragments bound to MHC class I or class II molecules

Question 6

biochemical characterization of TCR

Answer 6

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

Question 7

generating a diverse TCR repertoire

Answer 7

• recombination of different gene segments (V, D, J)
• recombination of different numbers of gene segments (TCR delta locus)
• imprecise joining of segments
• P and N nucleotide addition (TdT)
• assembly of different combinations of rearranged TCR chains (different a/b d/g combos)
• NO SOMATIC HYPERMUTATION
• but have many more V and J segments (in a/b)
• so actually more diverse than Ig cells

Question 8

Cytosolic pathogens

Answer 8

• degraded in cytosol
• peptides bind to MHC Class I
• presented to CD8 cells
• effect is cell death

Question 9

intravesicular pathogens

Answer 9

• degraded in endocytic vesicles (low pH)
• peptides bind to MHC class II
• presented to CD4 T cells
• effect is activation to kill the bacteria by macrophages or other phagocytotic cells

Question 10

extracellular pathogens and toxins

Answer 10

• degraded in endocytic vesicles (low pH)
• peptides bind to MHC class II
• presented to CD4 t cells
• effect is activation of B cells to secrete Ig to eliminate bacteria/toxins

Question 11

antibodies vs t cell receptors

Answer 11

• antibodies recognize surface structures

- t cell receptors recognize short peptide fragments from antigenic proteins

Question 12

features of TCR recognition of mMHC complex

Answer 12

-simulataneous recognition of MHC specificity and peptide specificity
-TCR affinity for peptide and MHC is weak relative to antibodies
Kd of 10^-5 to -7 vs 10^-7 to -11 (smaller Kd is more affinity)

Question 13

CD4 and CD8

Answer 13

• co receptors on T cells
• increase sensitivity to pMHC
• react with constant region of MHC class I (CD8) and II (CD4)
• TCR bound to peptide part of MHC, CD molecule bound to constant region

Question 14

superantigens

Answer 14

• bacterial enterotoxins-staph, strep, mycobacterial
• minor lymphocyte stimulating antigens (endogenous mouse retroviral products)
• unidentified endogenous antigens

Question 15

staph-S aureaus

Answer 15

• food poisoning, shock-enterotoxins A, B, C1,2,3, D and E
• TSS (toxin TSST1)
• scalded skin syndrome-exfoliating toxins A and B

Question 16

S pyogenes

Answer 16

• pyrogenic exotoxins ABC

- fever, rash, shock

Question 17

M arthritides mitogen

Answer 17

-shock

Question 18

superantigens 2

Answer 18

• bind to outside of MHC/TCR complex and undermine it’s specificity
• leads to release of too many cytokines-shock/death
• have specificity for Vbeta regions of MHC complexes
• increase number of responsive t cells from 1 in 10^4 to 5 to 1 in 4 to 20
• feel like shit

Question 19

MHC genes

Answer 19

• DP
• DQ
• DR
• heterodimers
• class I HLA a, B, C
• class II HLA D
• highly polymorphic (DRbeta has many more alleles because alpha only has 3)

Question 20

MHC recognition

Answer 20

• needs both self and right protein to recognize–watch this part of lecture again
• cross reactivity is foreign peptide/self MHC, peptide dominant, or MHC dominant binding
• needs to see self MHC/foreign protein??***

Question 21

MHC class I

Answer 21

• on all nucleated cells
• monitor cytoplasm
• need them if something in brain goes wrong- want to kill them with CD8

Question 22

MHC class II

Answer 22

• subset of hematopoietic cells and thymic stromal cells
• only need to find toxins/ bacteria/ intravesicular
• cells that will secrete cytokines

Question 23

MHC class I structure

Answer 23

• alpha 1, 2, 3
• Beta 2 microglobulin
• -monomeric/folds on itself
• protein binding pocket

Question 24

MHC class II structure

Answer 24

• alpha 1, 2
• beta 1,2
• up and down pairs
• 2 chains instead of one
• peptide binding cleft

Question 25

peptide binding grooves

Answer 25

-MHC class II is more open- can take bigger peptides than class I (12-14 or bigger vs 8-10)

Question 26

MHC class II processing pathway

Answer 26

• antigen taken up into vesicles
• in early endosomes, neutral pH, proteases inactive
• acidification activates protease, cleaves antigen into fragments
• vesicles containing MHC class II molecules fuse with vesicles containing peptides

Question 27

MHC class I processing pathway

Answer 27

• protein, proteosome, TPP II, Aminopeptidase, TAP, ERAAP

- protein degraded by proteosome, goes to ER, gets put on MHC, goes through golgi to surface