T cell Development (Week 6) Flashcards
Where do T cells develop?
- thymus
- T-cell precursors travel from the bone marrow to develop in the thymus
- mature T-cells leave thymus and travel to secondary lymphoid tissues
T-cell development and pre-TCR
- 𝛼β T cells, not γ𝛿 T cells, express
CD4 or CD8, they make a pre-TCR - γ𝛿 T cells do not undergo selection and do not make a pre-TCR
Pre-TCR
rearranged β chain with a
surrogate 𝛼 chain (pT𝛼)
𝛼β T cells development is favoured…
- β commitment occurs after
successful rearrangement of β chain,
while γ𝛿 needs both chains to undergo successful rearrangement - There are two chances
for successful rearrangement of each β chain loci
Checkpoint 1: Formation of Pre-TCR (𝛼β)
- β chain rearrangement is tested through binding surrogate 𝛼 chain (pT𝛼) and forming a functional pre-TCR
- Successful formation of functional TCR = proceeding to next stage of development
- Unsuccessful = apoptosis
𝛼 Chain Rearrangement
- 𝛼 chains only require one
recombination event - Can make several attempts to
rearrange the same gene - Successful 𝛼β rearrangement = no more γ𝛿 rearrangement
Checkpoint 2: Formation of Functional 𝛼β TCR
- Successful 𝛼 chain rearrangement commits T cell to 𝛼β fate
- successful 𝛼 chain rearrangement to form function TCR or cell undergoes apoptosis
MHC proteins and T cells
- T cells recognize peptides
bound to MHC molecules - MHC genotype restricts the
antigen specificity of the T cells
Positive selection of 𝛼β T Cells
- undergo positive selection first
- Must bind self MHC molecules to be
able to recognize peptides presented
on our own cells - No self-MHC recognition = apoptosis
Negative selection of 𝛼β T Cells
- eliminates highly self-reactive T cells
- Autoreactive T cell strongly binding to pAPCs in the thymus result in apoptosis = central tolerance
MHC recognition and T cells
- Recognition of either MHC Class I or MHC Class II commits cell to become single positive for CD8 (Cytotoxic) or CD4 (Helper)
- T cells become MHC restricted
AIRE (Autoimmune regulator) protein
- mediates the expression of organ
peptides in thymus - under control of the AIRE protein, thymic medullary cells express tissue-specific proteins, leading to deletion of tissue-reactive T cells
- in absence of AIRE, T cells reactive to tissue-specific antigens mature and leave the thymus
Anergy
unresponsive to antigen
How T cells be made anergic?
T cells that bind self-peptides can be made anergic either through binding incorrect receptor combination or binds inhibitory receptors
Suppression of Autoreactive T cells by Tregs
Recognizes MHC Class II on pAPC
presenting self-antigens and blocks
CD4 T cell that recognizes this from
getting activated
