T Cell Receptor Flashcards
1
Q
Structure of T cell antigen receptor
A
- 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
Q
T cell and B cell recognition of antigen
A
- 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
Q
Biochemical characterization of the TCR
A
- disulfide linked heterodimer
- transmembrane protein
- constant and variable regions
- both chains are glycoproteins
4
Q
Generating a Diverse TCR Repertoire
A
- 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
Q
Diversity in antibodies and TCR
A
-total potential diversity in Ig- ~10^11
in TCR alphabeta ~10^16
-in TCR gammadelta ~10^18
6
Q
T cells monitor the intracellular environment of the host cell
A
- 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
Q
TCR recognition of MHC complex
A
- 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
Q
CD4 and CD8
A
- 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
Q
Superantigens
A
- bacterial enterotoxins- staphylococcal, Streptococcal and Mycobacterial
- Minor Lymphocyte stimulating MIs antigens- Endogenous mouse retroviral products
- unidenified endogenous antigens
10
Q
Diseases caused for superantigens
A
- 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
Q
SEB/ TCR/ MHC
A
- 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
Q
Gene structure of human MHC/HLA
A
- 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
Q
Differential tissue expression of MHC molecules
A
- 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
Q
Structure of MHC I
A
- 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
Q
Structure of MHC II
A
- 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
