(L22) Antigen Capture and Presentation Flashcards
MHC class I
What genes are in this locus? Where is it expressed? How large of a peptide does it hold? What is its function? What is its structure and where do Ags bind?
Locus:
-HLA-A, HLA-B, HLA-C
Expressed on all nucleated cells
Peptides 8-10 AAs in length
Functions:
- presents to CD8+ CTLs
- inhibits NK cells
Structure:
-α chain is membrane bound (HLA encoded) with 3 domains
—Ag binding grove between α1 and α2
-β-micoglobulin (non-HLA encoded)
MHC class II What genes are in this locus? Where is it expressed? How large of a peptide does it hold? What is its function? What is its structure and where do Ags bind?
Locus:
-HLA-DP, HLA-DQ, HLA-DR
Expressed on professional APCs
Peptides 13-18 AAs in length
Functions:
-presents to CD4+ helper T cells
Structure:
- α and β chain are both membrane bound and contain 2 domains
- Ag binds between α1 and β1 domains
What does the term MHC restriction mean?
L22 S27
MHC class I only presents to CD8+ T cells via association between α3 domain of MHC I with CD8
MHC class II only presents to CD4+ T cells via association between β2 domain of MHC II and CD4
What are the APCs? When do they express MHC class II and what if anything stimulates this?
L22 S29
Dendritic cells:
- MHC class II constitutively expressed
- increased via maturation and IFN-γ
Macrophages:
- MHC class II NOT constitutively expressed
- induced by IFN-γ
B-cells:
- MHC class I constitutively expressed
- increased by IL-4
How do dendritic cells (both classical and plasmacytoid) capture and present antigens?
Where does each step occur?
What is the difference of antigen types with each?
L22 S30
Classical DCs (tissues):
- capture Ag in tissues and lose adhesion
- migrate to lymph nodes and matures while migrating (expression of CD80/B7)
- presents MOST Ags to T cells in the lymph node
Plasmacytoid DCs (blood and tissues):
- capture Ag in blood
- migrate to the spleen and matures while migrating (expression of CD80/B7 and production of Type I interferons)
- primarily presents VIRAL Ags to T cells in the spleen
What are the steps of the class II MHC loading pathway? What types of antigens are loaded?
L22 S34-35
Exogenous proteins are ingested and degrades through the lysosome.
MHC II is assembled into the ER (CLIP blocks native ER proteins from binding CLIP)
MHC II is transported from ER to golgi and then to endosome containing degraded Ags.
HLA-DM degrades CLIP allowing loading of MHC II
Loaded MHC II is fused with cell membrane and presented
What are the steps of the class I MHC loading pathway? What types of antigens are loaded?
L22 S36
Endogenous antigens are degraded by the proteasome.
Degraded proteins are transported into the ER by TAP.
Degraded proteins are loaded into MHC I (synthesized in the ER)
Loaded MHC I is transported to the Golgi and then to the cell membrane where it is presented
What is cross presentation?
L22 S37
Phagocytic APCs ingest viral infected cells or tumor cells.
Ags are loaded onto MHC I instead of MHC II and presented to CD8+ cells instead of CD4+ cells
What is the result of antigen presentation to T cells?
L22 S38
Macrophage MHC II presentation:
-CD4+ T cells releases cytokines that activate killing of phagocytosed microbes
B cell MHC II presentation:
-CD4+ T cells release cytokines that stimulate antibody secretion
MHC I presentation from any cell:
-CD8+ T cells kill infected Ag-presenting cell
What gene is associated with ankylosis spondylitis?
L22 S42
HLA-B27
What is the cause of bare lymphocyte syndrome class I?
L22 S45
Nonfunctional TAP protein preventing proteins from entering the ER to be loaded onto MHC class I
What is the cause of bare lymphocyte syndrome class II?
L22 S46
Deficiency of HLA class II expression mostly due to lack of relevant transcription factors.
Transcription factors:
- CIITA
- RFX5
- RFXAP
- RFXANK
What HLA gene is associated with rheumatic fever?
L22 S43
HLA-DR4
What HLA gene is associated with Sjörgrens syndrome?
L22 S43
HLA-DR3
