Lecture 21: Antigen Capture and Presentation Flashcards
Class I MHC genes
- encoded by 3 different regions in locus
- HLA-A/B/C
- on all NUCLEATED CELLS
- present to Cytotoxic T-Lymphocytes
- inhibitory receptor for NK cells
Class I MHC structure
- heterodimer of two proteins
- alpha chain (MHC encoded)
- membrane bound glycoprotein
- beta2 microglobulin (non MHC encoded)
- associates non-covalently with alpha3
Class II MHC genes
- encoded by HLA-D region
- membrane bound glycoproteins
- on antigen-presenting cells
- presents to CD4+ T cells
HLA peptide binding
- low affinity interaction (slow on rate, very slow off rate)
- allows complex time to interact with T-lymphocytes
H-Y (minor MHC/HLA)
- coded on Y chromosome
- associated w/acute rejection of male grafts in female recipients
What domains on the MHCI/II complexes do CD8 and CD4 recognize?
CD8 –> binds to alpha3 domain on MHCI
CD4 –> binds to beta2 domain on MHCII
What T cells do dendritic cells, macrophages, and B lymphocytes present to?
DC –> naive T cells (initiation of T cell responses to protein antigens)
Macrophages –> CD4+ effector T cells (effector phase of cell-mediated immune response)
B lymphocytes –> CD4+ T helper cells (humoral immun response)
Plasmacytoid Dendritic Cells
- found in blood/tissue
- promote innate anti-viral state (produce Type 1 interferons)
- expresses TLR 7 and 9
Dendritic Cell Activation
- lose adhesion markers and upregulate CCR7
- inc. MHC and CD80 expression
- travels to 2nd lymphoid tissue
- mature as migrate
Ankylosing Spondylitis
- spine inflammation
- 88% express HLA-B27 allele
- cannot bind critical antigenic peptide
Rheumatic Fever
- Abs for streptococci cross react with cardiac tissue
- patients w/HLA-DR4 more likely to develop
Bare Lymphocyte Syndrome
- TAP protein nonfunctional, peptides can’t enter ER
- cells cannot present antigens
symptoms: chronic respiratory infections, poor responses to viruses
Bare Lymphocyte Syndrome Class II
- inherited defect in CIITA (deficiency in HLA Class II expression, non-functioning T lymphocytes)
- HLA II genes turned on by CIITA, RFX5, RFXAP, RFXANK
- mutations in these Transcription Factors lead to dec. expression of Class II gene products