Flashcards in T and B cell Development Deck (25):
What are the components of a TCR?
2 polypeptide chains, one alpha, on beta OR one gamma and one delta; They are not isotypes. T cells do NOT change their TCRs and they are not secreted.
Do both CD4 and CD8 cells have alpha/beta TCRs?
Do gamma/delta TCRs bind to MHC 1 or 2?
What is the goal of TCR production?
To produce a TCR alpha or beta chain polypeptide with 2 regions; Variable region and a constant region.
Describe the problem and solution to TCR production.
Germline DNA contains exons that encode the constant regions but does NOT contain exons that encode variable regions. Therefore, DNA is rearranged to form an exon that will encode a specific variable region.
What is required in TCR production?
1. Enzymes that can cut, bend and repair DNA; RAG, Tdt, DNA-PK and other enzymes.
2. Specific regions of DNA that can be manipulated; V, D and J gene segments.
What genes are needed to make the beta chain?
V, D, J make the variable region. C makes the constant region.
What genes are needed to make the alpha chain?
V and J make the variable region. C makes the constant region.
What does RAG1 and 2 do?
They bind to the gene segments, cut the DNA, and join the gene segments together; Without these enzymes, antibody and TCR can not be made nor can mature B and T cells.
What does TdT do?
It adds random nucleotides (N nucleotides) to the ends of gene segments that have been cut by RAG before the gene segments are attached together; Active in pro-B and pro-T cells; Adds junctional diversity.
What is the role of DNA repair enzymes?
They help seal the junctions; Can change nucleotide sequence at junctions during repair. (Junctional Diversity)
What is the benefit of cutting and rearranging DNA for TCRs?
Random combinations of V, D, and J gene segments and junctional diversity increase the chance that we will produce a B or T cell with an antigen receptor that is specific for the pathogenic antigens we are exposed to.
What are the two functional requirements of a T cell?
1. It must have a TCR that will bind to MHC
2. It must have a TCR that will NOT bind to self antigens.
When is the decison point between becoming a CD4 or CD8?
The decision is not made until the transition from an immature T cell to a mature T cell.
KNOW the T cell development chart
ON page 61.
What is the disadvantage to random VDJ rearrangement?
Reactivity to Self
What happens to an autoreactive B or T cell?
1. Destroy the autoreactive cell.
2. Change the autoreactive cell.
3. Suppress the autoreactive cell.
Explain Central tolerance vs Peripheral tolerance.
The repression of autoreactive cells in the bone marrow or thymus (Central tolerance). If its in the lymphoid tissues/organs (peripheral tolerance)
Describe the components of an antibody molecule.
Made of 4 polypeptide chains: 2 identical heavy chains and 2 identical light chains that are connected by disulfide bonds.
Describe the makeup of a heavy chain.
One variable region (VH); contains amino acids that bind to a specific epitope on an antigen. Also has a constant region; Determines effector function of antibody.
What is an epitope?
A specific region of an antigen that antibodies (or TCR) bind.
What are the different types of heavy chain?
Mew, delta, gamma, alpha, epsilon; Each individual antibody molecule has one type.
Describes the components of the light chain.
One variable (VL) and on constant (CL) region; Two different types of light chain, kappa and lambda. Each individual antibody molecule has one type.
What does the Fc region do?
It determines the antibody's isotype. All antibodies have a kappa or lambda connected to a mew, delta, gamma, alpha or epsilon heavy chain; This makes IgM, D, G, A, or E respectively.