was based on eight MHC sequences: 1. The dendrogram of gene relatedness below HL
ID: 219969 • Letter: W
Question
was based on eight MHC sequences: 1. The dendrogram of gene relatedness below HLA-A2, HLA-A31, HLA-B1501, HLA-A1101, HLA-DQ8alpha, HLA-DQ8beta, HA C12, HLA-E Using your knowledge of the polygenic and polymorphic nature of MHC molecules, write a likely HLA designation from the list above for each of the eight sequences designated 1-8 below. Circle the sequences that demonstrate the "polymorphic nature" (allelic variation at a single gene locus) of MHC. 2. Is HLA-E more similar to MHC class I or class ll proteins?- 3. HLA-E helps to identify cells that have been manipulated to make little HLA-A HLA-B and HLA-C because they are virally infected. HLA-E interacts with receptors on which innate immune cell type: txExplanation / Answer
2)HLA class I histocompatibility antigen, alpha chain E (HLA-E)also known as MHC class I antigen E is a protein that in humans is encoded by the HLA-Egene. The human HLA-E is a non-classical MHC class I molecule that is characterized by a limited polymorphism and a lower cell surface expression than its classical paralogues. The functional homolog in mice is calledQa-1b, officially known as H2-T23.
Structure
Like other MHC class I molecules, HLA-E is a heterodimer consisting of an ? heavy chain and a light chain (?-2 microglobulin). The heavy chain is approximately 45 kDa and anchored in the membrane. The HLA-E gene contains 8 exons. Exon one encodes the signal peptide, exons 2 and 3 encode the ?1 and ?2 domains, which both bind the peptide, exon 4 encodes the ?3 domain, exon 5 encodes thetransmembrane domain, and exons 6 and 7 encode the cytoplasmic tail.
3)HLA-E has a very specialized role in cell recognition bynatural killer cells(NK cells). HLA-E binds a restricted subset of peptides derived from signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G. These peptides are released from the membrane of theendoplasmic reticulum (ER) by the signal peptide peptidase and trimmed by the cytosolicproteasome. Upon transport into the ER lumen by the transporter associated with antigen processing (TAP), these peptides bind to a peptide binding groove on the HLA-E molecule. This allows HLA-E to assemble correctly and to be expressed on the cell surface. NK cells recognize the HLA-E+peptide complex using the heterodimeric inhibitory receptor CD94/NKG2A/B/C. When CD94/NKG2A or CD94/NKG2B is engaged, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis. However, binding of HLA-E to CD94/NKG2C results in NK cell activation. This interaction has been shown to trigger expansion of NK cell subsets in antiviral responses.
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