L11_T-Cell Receptor Flashcards
What does MHC stand for?
Major Histocompatability Complex
How do cells monitor what is going on inside of them and communicate this to the outside world?
peptide presenting MHC molecules
Describe the difference in how B-cells and T-cells recognize antigen
B-cells recognize the native form of the foreign antigen in its 3D structure. They can recognize protein, carbohydrate or lipids. T cells recognize short peptide sequences presented by MHC that can originate form anywhere in the foreign protein. T- cells only recognize protein
describe the biochemical characterization of TCRs
Disulfide linked heterodimer, transmembrane protein, constant and variable regions in both chains, Both chains are glycoproteins
Is there more diversity in TCR or BCRs
TCR
What MHC class generally presents the following pathogens on the cell surface? Cytosolic, Intravesicular, Endocytosed extracellular
MHC1, MHC2, MHC2
What has stronger affinity for its target, TCR or Antibody?
Antibody
How do TCRs help increase sensitivity for their targets?
CD8 and CD4 recognize specific MHC
What do CD4 and CD8 recognize and are they dimers or monomers?
CD4 recognized MHCII and is a monomer. CD8 recognizes MHCI and is a heterodimer.
What region of the MHC receptors does CD4 and CD8 recognize?
The constant region of MHC molecules.
Describe the difference of how gamma delta recognized antigen compared to alpha beta
gamma delta recognize much more similar to a BCR by recognizing the 3D antigen even if it is not attached to MHC but is still acting as a TCR.
How do superantigens work? what is one species that is well known for producing superantigens.
Staph Aureus enterotoxin. Superantigens glue together TCR and MHC molecules in a non specific manner which causes a massive cytokine storm which leads to shock. Some people are more susceptible than others. generally bind to Vbeta domain of TCR. Superantigens can cause 1 in 4 T-cells to respond to MHC compared to 1 in 1000-10000 in a normal immune response
Identify MHCI and MHCII as monomer or dimer
MHCI is a 3 subunit monomer that interacts with Beta2 microglobulin. MHCII is a heterodimer (alpha and beta)
Identify the HLA genes that make up Class 1 and 2 MHC molecules
MHCI - HLA-A, HLA-B, HLA-C
MHCII - HLA-D alpha and beta chain (Subclasses DP, DQ, DR)
What is the purpose of the DO and DM genes of MHCII
They help with loading the peptide onto the other (DR, DP, DQ)
Where is there more diversity, in the individual alpha beta genes of the MHCII or in the A, B, or C genes of MHCI
A,B, and C of MHCI because thats all you get. There is now diversity from combination of two chains like in MHCII
Describe how the TCR sees the peptide sequence and MHC structure differently
It sees the 3D structure of MHC and the linear AA sequence of the protein fragment.
What cells express MHCI
All nucleated cells
What cells express MHCII
subset of hematopoietic cells and thymic stromal cells: B-cells, Macrophages, Other APC (langerhans and dendritic) and epithelial cells of the thymus
What are the 3 requirements for presentation of MHCI
- Beta2 Microglobulin
- Properly folded monomer
- Peptide in binding groove
What subunits of MHCI create the binding groove?
alpha 1 and alpha 2
What subunits of MHCII create the binding groove in MHCII
alpha 1 and beta 1
What is the major difference between the binding groove in MHCI and MHCII?
MHC1 binding groove is closed off at either end which restricts the length of the peptide to smaller fragments (8-10AA). The MHCII binding groove is open and can house large and more variable peptide chains (at least 12-13AA)
What are the vesicles called that carry MHCII molecules and fuse with endolysozomes that contain antigen
M2C vesicles.
How do MHCI molecules come into contact with antigen peptides?
Cytosolic proteins are broken down by proteosome. ATP-dependent TAP moves these peptide into the ER where the MHCI molecule is help inactivated by chaperones. THe peptide binds, the chaperones release, and the MHCI is moved to the cell membrane through default pathway.
does affinity maturation occur with T-Cells?
NO
What is the primary function of a T-cell?
To monitor the intracellular environment of the host cell.
State whether MHC I and II are monomers or dimers
MHC I is a monomer, MHC II is a dimer
To what portions of the MHC and TCR do super antigens bind?
The variable regions. Specifically the Vbeta of the TCR
