Antigen Capture and Presentation Flashcards
What is the difference in location between the two types of Major Histocompatibility Complex (MHC)/HLAs?
Type I is found on all nucleated cells. Type II is found on professional antigen presenting cells (dendritic cells, macrophage, B lymphocytes, and some thymocytes).
What is histocompatibility?
Whether a transplanted tissue will be accepted as self or not.
What are the gene regions that encode for HLA I and HLA II?
HLA I: HLA-A, HLA-B, HLA-C
HLA II: HLA-D
What are the specific cells that HLA I and HLA II present to?
HLA I: CD8+ cytotoxic T-lymphocytes (CTL)
HLA II: CD4+ T-lymphocyte
What is the difference between the peptide binding groove found in HLA I and HLA II?
HLA I: Between α1 and α2 domains. Binds peptides about 8-10 amino acids in length. Closed ends limit size.
HLA II: Between α1 and β1 domains. Binds peptides 13-18 amino acids in length. Open ends allow larger peptides to bind.
What is the difference in diversity between HLA I and HLA II?
HLA I: Has 6 different HLA alleles that can be expressed at the same time on each cell.
HLA II: Has 6 α-chains and 6 β-chains (3 from mother and 3 from father) that can be expressed at the same time on each cell. Any α-chain allele may associate with any β-chain allele. Greater diversity.
Describe the synthesis of HLA I.
Proteasome degrades cytosolic protein. TAP transports peptides to ER. α-chain translated into ER as glycoprotein. In ER, α-chain interacts with β2-microglobulin (non-HLA encoded). HLA I then associates with degraded peptide. HLA I/peptide complex is transported to the cell surface.
What is the clinical significance of H-Y?
It is an antigen coded on the Y chromosome. Associated with acute rejection of male grafts in female recipients.
Where are antigens filtered?
If entering via the periphery, they are filtered by the lymph and lymphoid tissues. If in the blood, they are filtered by the spleen.
Describe how HLA II and costimulators are expressed in dendritic cells.
Both are expressed constitutively, but increases with IFN-γ. Costimulators increased with TLR binding.
Describe how HLA II and costimulators are expressed in macrophages.
Both are expressed in low numbers initially, but are increased with IFN-γ. Costimulators increased with TLR binding.
Describe how HLA II and costimulators are expressed in B lymphocytes.
HLA II is expressed constitutively, but increased by cytokines. Costimulators are induced by T cell antigen receptor cross linking.
Explain how DC are activated and how they present to T cells.
Once an antigen is captured, it loses adhesive markers and begins traveling to secondary lymphoid tissue. They mature as they migrate, and present antigen to T cells upon arrival.
Describe the synthesis of HLA II.
Exogenous proteins are ingested and degraded. α/β chains and invariant chain are synthesized in the ER and transported through the golgi. Peptide is not loaded until late endosomes. Invariant chain is degraded so CLIP remains. HLA-DM switches out CLIP for peptide. Sent to cell surface.
What is ankylosing spondylitis?
Inflammation of the spine. Individuals with this disease usually express the HLA-B27 allele.
