T Cells Flashcards
T cell receptor
an alpha and beta chain with a variable and constant region
all T cells express _
a T cell receptor (TCR)
all TCR’s are expressed in association with _
CD3
CD3
signal transducer for TCR’s
TCR recognizes _
MHC-I or MHC-II proteins
alpha chain of TCR is analogous to _
antibody (B cell) light chain
beta chain of TCR is analogous to _
antibody heavy chain
TCR differences from BCR
does not undergo somatic hypermutation and no affinity maturation
MHC Class I structure
an alpha chain with 3 external domains and 1 beta-2 microglobulin domain
beta-2 microglobulin domain
no transmembrane region, no cytoplasmic tail, not encoded in MHC (gene)
MHC Class II structure
two alpha domains and two beta domains
MHC-I peptide binding cleft
2 alpha domains
MHC-II peptide binding cleft
1 alpha and 1 beta domain
MHC-1 tissue distribution
all nucleated cells and RBC’s in some species (not human)
MHC-II tissue distribution
only on antigen presenting cells - macrophages, dendritic cells, B cells, thymic epithelium
MHC-I function
presents antigens to CD8+ cells
MHC-II function
presents antigens to CD4+ cells
MHC-I cells
T cells, B cells, macrophages, neutrophils, other nucleated cells (like hepatocytes)
MHC gene structure
contains a DP, DQ, and DR region for class II; contains an HLA-A, HLA-B, HLA-C for class I
MHC-II pathway
exogenous antigen –> endocytic vesicle –> peptide production in phagolysosome –> peptide binds MHC-II –> MHC-II presents to CD4+
MHC-I pathway
endogenous antigen –> proteasome degrades to peptides –> peptide transport into ER –> peptide binds MHC-I –> presents to CD8+
Tap1/Tap2
transports peptides into ER from proteasome in MHC-I pathway
adhesion molecules between T cell and target cell
LFA-1 on T cell and ICAM-1 on target cell
what binds to MHC?
TCR-CD3
thymocyte migration
DN1 in medulla –> DN2 in cortex –> DN3 –> DN4 –> immature double-positive thymocyte –> mature CD8 or CD4 (back in medulla)
DN1
CD44+; adhesion
DN2
CD44+, CD25+; adhesion and IL-2 receptor
DN3
pre-TCR; little of CD44 and CD25
DN4
no CD44 or CD25
pre-T cell receptor
beta chain rearranges first then alpha chain
pre-TCR signaling
stops beta-chain rearrangement and initiates alpha chain rearrangement –> down-regulates CD25 and up-regulates CD4/CD8
thymic selection
positive selection of cells whose receptor binds MHC molecules and death of cells that do not –> then negative selection of cell with high affinity for self antigen
When does positive selection occur?
at CD4+/CD8+ stage
When does negative selection occur?
at CD4+/CD8+ stage and at single positive stage
mTEC
medullary thymic epithelial cell; promiscuous gene expression (AIRE)
AIRE
autoimmune regulator; transactivator of tissue-specific gene expression which allows negative selection against T cells reactive to tissue-specific antigens
