Lecture 11 Flashcards
What are the goals of T cell development
- Generate functional TCRs
- Make T cells that are self-MHC restricted (positive selection)
- MHC specificity–> CD4 = MHC II, CD8 = MHC I
- Eliminate T cells that are self recognizable (negative selection)
Where does T cell development happen?
Develops in the thymus
-comes from common lymphoid progenitor
-T cells form in bone marrow and develop in thymus
What is DiGeorge Syndrome?
Lack of thymus
-recurrent infections due to lack of T cells
The thymus is critical for the development of?
Bone marrow derived T cell precursors
What is SCID mutation?
Does not have the gene required for somatic recombination
What is Nude mutation?
Does not have gene required for thymus formation
Which is long lived/ self renewing, B cells or T cells?
T cells
What are the important cells in the Thymus?
- Thymocytes–> Developing T cells
- Cortical epithelium cells (cTECs)
- Medullary epithelium cells (mTECs)
- Dendritic cells
- Macrophages
Which cells in thymus do not have hematopoietic origin and which origin does it have instead?
-Cortical epithelium cells (cTECs)
-Medullary epithelium cells (mTECs)
-Stromal cell origin
How does CD4 and CD8 expression occur in the dot plot?
- Common lymphoid progenitor starts off DOUBLE NEGATIVE has no CD4 or CD8
- Common lymphoid lymphoid matures DOUBLE POSITIVE
- Common lymphoid progenitor then differentiates into CD8 SINGLE POSITIVE or CD4 SINGLE POSITIVE
Double positive is only in?
Thymus
What is the first check point of T cell development
Functional Pre-TCR (double negative)
-Surrogate alpha chain is encoded in germline
-once Beta chain has been successfully rearranged, rearrangement of further genes stop
What happens if the Beta chain has been successfully rearranged? What do the new receptors signal for?
- Stopping TCR beta rearrangement (Allelic exclusion)–> no more RAG protein
- Copies succesful receptors (proliferation)
- Differentiation into next stage of development (C4 and CD8 development)
What happens in second checkpoint of functional TCR?
Functional TCR (Double positive)
-Thymocyte is double positive
-Alpha chain rearrangement begins
-alpha and beta chains are brought together
What is required for transducing both TCR and pre-TCR signaling?
CD3
What is positive selection?
Make a T cell that is self-MHC restricted
What does it mean to be MHC restricted?
T cells and its progeny will recognize specific peptide ONLY when presented by the MHC isoform/allele that positively selected it
What happens if there is positive selection?
When MHC complex is recognized the thymocyte is rescued from programmed cell death–>converts to single positive
What happens if there is no positive selection?
Failure to recognize MHC complex
-Apoptotic cell death due to neglect
-TCR cannot bind at all/will not be activated by dendritic cells
During positive selection what do MHC II develop into?
CD4SP (SINGLE POSITIVE)
During positive selection what do MHC I develop into?
CD8SP (SINGLE POSITIVE)
What does a single positive thymocyte with normal MHC II express?
BOTH CD8 and CD4 mature T cells
What does a single positive thymocyte with normal MHC II negative mutant express?
ONLY CD8 mature T cells
What inhibits TCR?
TCR is inhibited when transgene expressed
What does a transgenic MHC I express?
Single positive CD8 T cells
What does a transgenic MHC II express?
Single positive CD4 T cells