what are the two major classes of T cells
cytotoxic CD8 T cells
helper CD4 T cells
The T cell receptor
primarily bind polypeptides never secreted incidence detector no effector function interacts with MHC complex antigens not recognized in isolation(must bind MHC for signal)
what are the two classes of T cell receptors
alpha: beta
gamma: delta
alpha:beta T cells
classic T cell adaptive immunity common in circulation not tissues develops and matures in thymus positive and negative selection
gamma:delta T cells
not involve in adaptive immunity monitor tissue health common in tissues not circulation develops, but does NOT mature in thymus limited positive and negative selection -one class
alpha chain of T cell receptor
similar to light chain of Abs
V, J, C segments
-junctional diversity
beta chain of T cell receptor
similar to heavy chain of Abs
V, J, D, C
-junctional diversity
how many hypervariable/complementarity-Determining per chain?
3
TCR genes are rearranged by what enzymes?
RAG 1/2 complexes
deficient in RAG leads to no T cells
what has more total diversity between immunoglobulins and alpha:beta receptors?
alpha:beta T-cell receptors
why? T cell receptor genome is longer
What do TCRs require for signal transduction?
CD3
CD3 complex
mediates TCR signaling
-NO TCR expression without CD3 complex
What does the MHC do?
presents broken down antigens(peptides) to TCRs
MHC class I
found on nearly all cells **presents intracelluar antigen** alpha and beta2 microglobulin **-ER antigen loading** **CD8 co-receptor
MHC class II
internalized (phagocytosis)
- on antigen presenting cells ( macs, dendritics, and B cells)
- *vesicular ER loading**
- *CD4 Co-receptor
what is another name for MHC
human leukocyte antigen (HLA)
will TCRs bind both MHC class I and II?
yes, it is the co-receptor on the T cell that determines MHC class binding
what cell does not have any MHC complexes on its surface?
erythrocytes and neurons
where does loading occur for MHC class I?
in the ER
where does loading occur for MHC class II
VESICULAR ER loading
cells that express MHC class II can express MHC class I T/F?
true
MHC I: antigen loading in the ER
- heavy chain is stabilized by calnexin until beta 2 binds.
- heavy chain forms peptide loading complex with calreticulin, tapsin, TAP and ERp57
- TAP delivers intracellular peptide to Class I heavy chain forming mature MHC I molecule
- MHC class I dissociates from peptide loading complex and is exported from ER
The intracelluar antigen peptides are how many residues?
8-10
- trimmed before expression
- allows detection of intracellular infection
MHC I: cross presentation of endocytosed antigen
phagocytic cells that have endocytosed antigen will express both MHC I and II with the same antigen
why is cross presentastion important?
important for naive CD8 T cell activation
-also doesn’t allow for intracelluar pathogens to live inside phagocytic cells
MHC II: CLIP prevents self antigen presentation how?
- invariant chain blocks binding of peptides to MHC II in the ER
- once inside a vesicle the invariant chain is cleaved, leaving CLIP fragment bound
- CLIP blocks binding of MHC II in vesicle
- HLA-DM facilitates release of CLIP, allowing peptides to bind
what blocks bind of MHC II in the ER?
invariant chain
what blocks the binding of MHC II in the vesicle?
CLIP
what releases the binding of CLIP inside the vesicle?
HLA-DM
the T cell synapse
what dictates MCH specificity of T cells
the Co-receptors on the T cells
NOT the TCR
what MHC does a CD8 bind?
MHC I on any cell with intracelluar pathogen
what MHC does a CD4 bind?
MHC II on a APC
T cells have a direct and indirect effector function how?
(direct) CD8s bind intracelluar pathogen infected cell to die
(indirect) -CD4s bind to APCs to release cytokines
(indirect) -CD4s bind to B cells to differentiate into plasma cells to make antibodies
