Académique Documents
Professionnel Documents
Culture Documents
Pre-T cell
V-J
In the thymus
Thymus
express
MHC H2b
(Containing LCMV specific cytotoxic T cells)
Zinkernagel et al.
T cells only recognize targets expressing H-2b:
the MHC haplotype of the thymus determines their MHC restriction.
Most
thymocytes
express the
TCR transgene
Evidence for Negative Selection: self antigen and MHC are required
(CD8)
Most thymocytes
express the TCR
transgene
Thymocytes
reactive to
self-antigen
are deleted
during thymic
selection
Fetal thymic lobes are excised and place in culture. At this stage,
thymus contains mainly CD4-CD8- thymocytes. It is a good model
to study the details of thymic selections
No peptide on
MHC class I
molecules
leads to positive
selection
leads to negative
selection
Summary:
The surface expression of pre-TCR is important for
pre-T cell development. Pre-TCR will deliver
signals to stop further TCR chain rearrangement,
begin proliferation and CD4/CD8 expression, and
possibly start TCR chain rearrangement.
T cell maturation occurs in the thymus where MHC
restriction and self tolerance are achieved. (by
positive and negative selections)
MHC molecules and the interaction between
thymocytes and thymic stromal cells are important
for the development of mature T cells.
T Cell Activation
T cells are activated in the secondary lymphoid tissues
Ca2+
PKC
SLP-76
ZAP-70 phosphosylates
adaptor proteins that recruit
components of several signal
pathways
Expressed on
activated T cells
Two pathways
Lead to apoptosis
In T cells
Activation-induced
cell death (AICD)
Blood samples
Summary:
Two signals are required for full T cell activation, one
from TCR-CD3 interactions with MHC-peptide
complex, the other from CD28 interactions with B7
family proteins. Thus, CD28 and B7 family are called
co-stimulatory molecules.
Lack of co-stimulatory signals in T cells results in
clonal anergy or sometimes apoptosis.
What are superantigens?
Fas-mediated and activation-induced cell death are
used to remove activated T cells and maintain T cells
homeostasis.