L11, MHC and Antigen Presentation Flashcards
recap: what is antigen presentation and what is the significance of it?
antigen presentation is the process by which an antigen located on the surface of an APC (e.g., a macrophage), is presented to a naive T-cell
what are MHC proteins?
cell surface glycoproteins (except MHC-III) that bind antigens and display them to T cells bearing the appropriate TCR
function of MHC-I
presentation of cytosolic antigens to CD8+ cytotoxic T cells (Tc)
function of MHC-II
presentation of extracellular/vesicular antigens to CD4+ T helper cells (Th)
function of MHC-III
secreted proteins; not involved in antigen presentation to T cells. includes complement, innate immune cytokines
what are MHC gene products referred to in humans?
HLA (Human Leukocyte Antigens)
what are MHC gene products referred to in mice?
H2
what cells are MHC-I molecules expressed by?
nearly all nucleated cells of the body
what antigens does MHC-I present?
- endogenous antigens (derived from intracellular pathogens)
- exogenous antigens by cross-presentation (mostly done by DC cells)
what does the presentation of self-peptide on MHC-I mean?
that a cell is healthy and should not be targeted by CD8+ cytotoxic T cells
what does MHC-I gene encode?
a single alpha chain protein
what MHC-II molecules mostly expressed by?
professional antigen presenting cells (pAPCs)
what are the three pAPCs?
Dendritic cells, macrophages, B cells
what antigens do MHC-II present?
exogenous antigens (extracellular) to CD4+ T helper cells
what does each MHC-II gene encode?
both single alpha and beta chains
what are the three membrane-distal domains of MHC-I?
alpha 1,2,3 and Beta-2 microglobulin
what are the three membrane-distal domains of MHC-II?
alpha 1, alpha 2, beta 1, beta 2
define polygeny
multiple alleles
why is MHC diversity so great?
because of polymorphism within multiple alleles from one individual to another
polygeny + polymorphism = ….
great diversity
MHC genes are …. and exist in an individual and are …. expressed
polygenic
codominantly
what does a mismatch of HLA haplotypes lead to?
graft rejection
what does antigen processing lead to?
the degradation of the antigen into small antigenic peptides
what is the MHC-I peptide loading process?
- endogenous antigen is degreaded by the proteasome to yield small antigenic peptides
- peptides are transported into the endoplamic reticulum via TAP
- Calreticulin and tapasin bind to the MHC-I molecule, catalyzing the removal of the chaperone and binding of the antigenic peptide
- peptide-loaded MHC-I molecules are eventually brought to the cell surface
what is the MHC-II peptide loading process?
- invariant chain binds the MHC-II groove to prevent binding of endogenous peptides
- MHC-II-li complex traffics through the endocytic pathway
- within acidified endosomal and endolysosomal compartments, antigens are broken down with the help of proteases into small antigenic peptides (13-18 amino acids)
- the same proteases will degrade the invariant chain, leaving only a small fragment (CLIP) in the groove of the MHC-II molecule
- CLIP is removed and replaced by the antigenic peptide
- peptide-loaded MHC-II molecules are eventually brought to the cell surface
what happens during MHC-I cross presentation
- exogenous antigens are internalized by APC
- antigenic peptides are presented to CD4+ Th cells by MHC-II molecules
- antigen-activated Th cells then “license” DCs to present these antigens but on MHC-I molecules
- this activates CD8+ Tc cells
what cells are predominantly responsible for antigen cross-presentation?
dendritic cells
