4. You have generated different mutant Ag-presenting cell lines. Each mutant cel
ID: 209770 • Letter: 4
Question
4. You have generated different mutant Ag-presenting cell lines. Each mutant cell line cannot make a functional version of the indicated protein. For each cell line, indicate whether antigern presentation by MHC I, MHC I, both MHC I and I, or neither class of MHC would be affected Consider only conventional antigen presentation. Circle the best choice. Explain your reasoning by describing the specific role of that protein in the antigen presentation process. (10 pts) a. HLA-DM MHC I/MHC I1/both I and II/neither l or Explanation b. Calnexin MHC I/MHC II/both I and II/neither I or II Explanation: c. CD4 MHC1/ MHC II /both I and I/neither l or lI Explanation: d. Invariant Chair MHC I/MHC Il / both I and II / neither I orI Explanation: e. TAP-1 MHC I/MHC II / both I and II /neither I orI ExplanationExplanation / Answer
a) HLA-DM - MHC class II.
HLA-DM is a molecular chaperone. The genes for HLA-DM are present in the MHCII region. The genes code for the alpha and beta chains, which form the protein. It functions in lysosomes and endosomes cells of the immune system. It acts APCs such as macrophages, dendritic cells and B cells by interacting with MHC class II molecules. It protects the MHC class II molecules from breaking down and regulates which proteins or peptides bind to them. It is essential for the immune system to respond effectively to a foreign invader.
b) Calnexin - MHC class I.
Calnexin acts as a chaperone for the folding of MHC class I -chain in the membrane of the endoplasmic reticulum. It binds to MHC I, maintaining them in a partly folded state.
c) CD4 - MHC class II.
CD4 is a co-receptor of the T cell receptor. It helps in the communication with antigen-presenting cells. Both T cell receptor complex and CD4 each bind to separate areas of the antigen-presenting MHCII molecule - 1/1 and 2. It interacts with the 2-domain of MHC class II molecules through its D1 domain. They are specific for antigens presented by MHC II and not by MHC class I.
d) Invariant chain - MHC class II.
The alpha and beta chains combine with each other and a third protein known as invariant chain in the rough endoplasmic reticulum. It helps in the stabilization of the complex. The alpha and beta proteins will not join together without the invariant chain. This chain trimerizes in the endoplasmic reticulum, which combines with MHC class II molecules. The invariant chain is proteolytically degraded and a peptide from the external protein combines with the MHC II molecule in the channel between the alpha-1 and beta-1 domains. The MHC II-peptide complex continues to the surface where it is expressed.
e) TAP-1 - MHC class I.
TAP-mediated peptide transport is a multistep process. The peptide-binding pocket is formed by TAP-1 and TAP-2. ATP binding to TAP-1 is the first step in the transport process. ATP bound to TAP-1, which induces ATP binding in TAP-2. It has also shown, which undocking of the loaded MHC class I is connected to the transport cycle of TAP caused by signals from the TAP-1 subunit.
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