Lecture 11 Flashcards
(23 cards)
How are antigens presented to T lymphocytes?
αβ T cells recognize antigens as peptide-MHC complex
What is antigen processing?
processed pathogen-derived proteins into peptide
What is antigen presentation?
peptide loaded onto MHC and present on cell surface
What is direct presentation?
cytosolic pathogens replicate in cytosol, antigens are processed/presented by MHC I to effector CD8+ T cells –> targeted killing by cytotoxic granules
How are intravesicular pathogens dealt with?
bacteria and some parasites taken up into endosomes –> antigens presented by MHC II to effector CD4+ T cells –> produce cytokines
How are extracellular pathogens and toxins dealt with?
proteins from pathogens bind to cell-surface receptors, enter vesicular system by endocytosis, presented by MHC II to CD4+ T cells
What is cross-priming?
dendritic cells present extracellular antigens on MHC I molecules, activating CD8+ T cell activation (via cytosolic or vesicular pathway)
How do B cells capture antigens?
using B-cell receptor (BCR) which allows precise internalization and processing in endocytic compartments
How do macrophages capture antigens?
engulf pathogens and debris through phagocytosis, break down in lysosomes, present processed peptides on MHC II to activate CD4+
How do dendritic cells capture antigens?
use endocytosis and macropinocytosis to take up antigens, process in lysosomes, load peptides onto MHC II. migrate to lymph nodes, present antigens to naive CD4+
What is the proteasome composed of?
20S catalytic core made of 4 multi-subunit rings, two 19S regulatory caps on each end
How does the proteasome degrade proteins?
E3 ligases tag proteins covalently with K48-linked polyubiquitin chains, 19S regulatory cap recognizes polyubiquitin and draws the tagged protein inside catalytic chamber, where it is degraded and released as peptide fragments
How is MHC class I molecule synthesized?
α chain synthesized in ER –> binds calnexin (chaperone that stabilizes) –> when β2-microglobulin binds, forms partially folded MHC I that dissociates from calnexin –> associates with TAP-associated complex (anchors in ER) –> peptides transported into ER by TAP –> binding of peptide completes MHC I folding –> dissociates from tapasin and peptide-loading complex –> exits via Golgi –> cell surface!
What comprises a TAP-associated complex?
Tapasin (links MHC I to TAP)
ERp57 (folding chaperone)
Calreticulin (folding chaperone)
What does ERAP1 do?
trim peptides that are too long so that they will fit into MHC I binding groove
What is TAP?
Transporter associated with Antigen Processing
How does MHCII peptide loading and presentation work?
antigens are taken up by antigen-presenting cells (APCs) like macrophages, dendritic cells, B cells –> initially contained in early endosome which matures and fuses with lysosomes, forming an acidified late endosome/phagolysosome –> V-type ATPase pumps H+ ions into vesicle lowering pH –> activates acid-dependent proteases (like cathepsins) –> proteases break down into smaller peptides –> MHCII pass through acidified vesicles where they bind peptide fragments –> moves to cell surface!
What is the purpose of MHC being polygenic?
everyone expresses multiple MHC molecules that can bind different sets, all MHCI/MHCII can present peptides to T cells, more peptides able to be presented
What is the purpose of MHC being polymorphic?
each MHC gene has different alleles in the population, even if a pathogen mutates to escape some MHCs, others will still recognize it
What is positive T cell selection?
T cells must recognize antigen only when presented by self-MHC, if they do not, they are eliminated
What is negative T cell selection?
T cells that strongly react to self-antigens are eliminated to prevent autoimmunity
What is alloreactivity?
1-10% of T cells are naturally cross-reactive, can recognize donor MHC as a self-MHC presenting antigen because positive selection allows weak MHC binders to survive
How do T cells recognize foreign MHC?
peptide-dependent: TCR recognizes foreign MHC because of the specific peptide it is presenting
peptide-independent: TCR recognizes structure of foreign MHC regardless of peptide
