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Flashcards in T Cell Receptor Deck (17)
1

Structure of T cell antigen receptor

-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

2

T cell and B cell recognition of antigen

-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

3

Biochemical characterization of the TCR

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

4

Generating a Diverse TCR Repertoire

-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

5

Diversity in antibodies and TCR

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

6

T cells monitor the intracellular environment of the host cell

-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

7

TCR recognition of MHC complex

-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

8

CD4 and CD8

-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

9

Superantigens

-bacterial enterotoxins- staphylococcal, Streptococcal and Mycobacterial

-Minor Lymphocyte stimulating MIs antigens- Endogenous mouse retroviral products

-unidenified endogenous antigens

10

Diseases caused for superantigens

-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

11

SEB/ TCR/ MHC

-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

12

Gene structure of human MHC/HLA

-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

13

Differential tissue expression of MHC molecules

-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

14

Structure of MHC I

-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

15

Structure of MHC II

-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

16

MHC II antigen processing pathway

-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

17

MHC I antigen processing pathway

-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