Please answer all the questions answering only one question is not helpful 13. i
ID: 217815 • Letter: P
Question
Please answer all the questions answering only one question is not helpful
13. in a TCR B chain, there are three hypervariable (HV) regions that are also referred to as CDRs.
a. what is hypervariable about there regions?
b. which of the HV regions is most responsible for interaction with an antigenic peptide?
14. what happens to a cell that is negatively selected ?
15. what about a cell would cause it to be negatively selected?
16. where does negative selection take place for t cells?
17. where does negative selection take place for B cells?
18.some immature T cells express both CD4 and CD8.
A. in what part of the body are these cells found?
b. About 80% of the T cells in the above location express both CD4 and CD8. What is the ultimate fate of most of these cells?
c. what is the usefulness to an immature T cell of expressing both of these molecules?
19. there are two possible ligh chains, encoded by two different genes, that can be used to make an antibody.
a. the one most commonly found in Ab molecules is the kappa chain. Why is this?
b. what is the other light chain?
20. for T cells, what is the function of positive slection?
21. using numbers, indicate the correct sequence of occurrence for the following steps in B cells development .
a.___ expression of a functional heavy chain protein
b.___expression of a functional light chain protein
c.___V-DJ recombination
d.___D-J recombination
e.___V-J recombination
f, ___ expression of a functional BCR
22. For each of the HV regions listed below, indicate the mechanism r mechanisms the underlie the varjability of amino acid sequinces that are found there. Your choices are combinatorial, junctional, or both.
A. HV1:
23. CTLA-4 is expressed on a number of different T cells.
a. give an example of a T cell that expresses it.
b. at what stage of the cell’s life cycle will it be expressed (e.g,before or after activation)
c. what is the function of this molecule?
24. clonal selection leads to activation of adaptive T lymphocytes and differentiation into effector cells.
a. where does clonal selection of T cells most commonly occur?
b. where does positive selection of T cells most commonly occur?
25. in secondary lymphoid tissues, after activation and differentiation of a CD+T cell clone the various daughter cells can have different fates.
a. the most common fate is to leave secondary lymphoid tissue as a helper cell, but another type of cell remains in the lymphoid tissue as a non-helper. What type (function) of cell?
b. another fate is to remain in the secondary lymphoid tissue as a helper cell but to migrate out of the T cell area to this other location
c. … as this type of helper cell.
26. compare and contrast clonal selection of T cells with positive slection of T cells with regard to the following.
a. what is the preprogrammed cell fate at the start of each process
(to die unless rescued or to live unless killed)?
for positive selection
ii. For clonal slection
b. what is the phenotype at the start of each process(double positive, single positive, or double negative)?
I. positive selection
ii. clonal selection
28. draw a linear diagram of a TCR B protein (no secanry or tertiary structure)
a. label the N terminus on the legt and the C terminus
b. label the different protein domains
c. within the V domain, label each section that is encoded by different gene segments by letter.
d. label the locations of the different HV regions (CDRs) by number.
e. label the C region domains .
Explanation / Answer
13. Complementarity-determining regions (CDRs) are part of the variable chains in T cell receptors, where these molecules bind to their specific antigen. TCR which is found on the surface of T-cells recognizes the antigenic peptides that are bound to MHC molecules. TCR polypeptide contains sites of increased aminoacid variability. There are four such sites, of which only three are CDRs (CDR1, CDR2, CDR3, HV4). The highly diverse CD3 region preferentially make contact with the antigenic peptide nestled in the MHC groove. HV4 does not normally contact antigen and, therefore, is not considered a CDR. Hypervariable region (HVR) a region of a GENOME that is made up of a variable number of repeated sequences and is diagnostic for an individual.
14-17:
Negative selection (central tolerance), is the process of eliminating any developing T or B lymphocytes that are reactive to self. It is essential for proper immune cell functioning because it helps ensure that mature B cells and T cells do not recognize self antigens as foreign microbes. T cell central tolerance occurs in the thymus (primary lymphoid organ). During negative selection, T cells are tested for their affinity to self. If they bind a self peptide, then they are signaled to apoptose (process of clonal deletion). Immature B cells in the bone marrow undergo negative selection when they bind self peptides. Properly functioning B cell receptors recognize non-self antigen or pathogen associated molecular proteins (PAMPs).
18. T cells that express both CD4 and CD8 are called double positive T cells found near the cortico medullary junction of thymus. Double-positive thymocytes (CD4+/CD8+) move deep into the thymic cortex, where they are presented with self-antigens. These self-antigens are expressed by thymic cortical epithelial cells on MHC molecules on the surface of cortical epithelial cells. Only those thymocytes that interact with MHC-I or MHC-II appropriately (i.e., not too strongly or too weakly) will receive a vital "survival signal". All that cannot (i.e., if they do not interact strongly enough, or if they bind too strongly) will die by "death by neglect" (no survival signal). This process ensures that the selected T-cells will have an MHC affinity that can serve useful functions in the body (i.e., the cells must be able to interact with MHC and peptide complexes to effect immune responses). The vast majority of all thymocytes end up dying during this process.
A thymocyte's fate is determined during positive selection. Double-positive cells (CD4+/CD8+) that interact well with MHC class II molecules will eventually become CD4+ cells, whereas thymocytes that interact well with MHC class I molecules mature into CD8+ cells. A T cell becomes a CD4+ cell by down-regulating expression of its CD8 cell surface receptors.