Activation of T Lymphocytes

dr. Widya Wasityastuti, M.Sc

wasityastuti@yahoo.com
Faculty of Medicine Universitas Gadjah Mada

Outlines
Development in primary
lymphoid organs

Activation in secondary or
peripheral lymphoid
organs

Outlines:

Structure of the T lymphocyte receptor

T lymphocyte development in the thymus

Positive and negative selection on T lymphocytes

Mature T lymphocytes migrate to secondary lymphoid

organs

T cell activation by antigen presenting cells

Differentiation of T lymphocytes effector cells

STRUCTURE OF T CELL
RECEPTOR
T cells

Membrane bound protein

with single antigen binding
site
4

TCR Complex
Complete functional receptor
complex contains :
heterodimers associated with
the six invariant accessory
chains - signalling protein [a
complex of four other signaling
chains -two , one , one collectively called CD3 and a
homodimer of chains]

ITAM (Immunoreceptor
tyrosine based activation
motifs)
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T CELL DEVELOPMENT
Immature T
cells

Mature T cells

Thymus

T cell development in Thymus

Generation of T cell receptors
Somatic gene rearrangements (recombination)
Expression of receptors in the cell surface

Selection of useful cells

Positive selection
Negative selection

The TCR - and -chain genes are composed of discrete

segments that are joined by somatic recombination during
development of the T cell

The germline organization of the human T-cell receptor

and loci generated by gene segment rearrangementassembly antigen specificity

10

The numbers of
human T-cell
receptor gene
segments and the
sources of T-cell
receptor diversity
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Proliferation of T cell precursor and somatic gene

rearrangement occur in the cortical region of the thymus
Failure in gene rearrangement will trigger apoptosis

Double
negative
thymocytes

T cell receptor CD4- CD8-

Double positive
thymocytes

T cell receptor
CD4+ CD8+

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Selection of useful cells: positive selection in the

thymic cortex
Double positive
thymocytes

Aims: to test whether TCR

properly interact with self MHC
molecules expressed in the
surface of thymic epithelial cells

Thymic epithelial cell

No interaction die
Thymic epithelial cell

Cortical epithelial cells

(stromal cells) express high
levels of MHC-I and MHC-II.

Interaction
survive
and become single
positive thymocytes
CD4+ OR CD8+

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Selection of useful cells: positive selection in the

thymic cortex
Single positive
thymocytes

Double positive
thymocytes
Double
positive
thymocytes

T cell receptor
CD4+ CD8+

Single positive
thymocytes

T cell receptor
CD4+ OR CD8+

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Selection of useful cells: negative selection in the

thymic medulla

Medullary APC expressing self molecules

Single positive
thymocytes

Aims: to test whether TCR can

recognize self molecules presented
by MHC molecules in the surface
of thymic medullary APC

Interaction die
(removal of self reactive cells)
No interaction survive

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Summary: T cell development in Thymus

Apoptotic cells are removed by macrophages
Somatic gene
rearrangement

Positive selection

Negative selection

Nave CD4+/CD8+ T cells (MHC restricted and self tolerant)

pass out the thymus to blood stream through venule or lymphatic vessels

16

Nave lymphocytes enter secondary lymphoid organs

from blood
There are T cells area in the secondary lymphoid organs
paracortex area in lymph nodes
interfollicular area in MALT
periarteriolar lymphoid sheet (PALS) in spleen

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Cellular traffic is orchestrated by chemotactic cytokines (chemokines) and

adhesion molecules which direct nave T cells out the blood and into
lymphoid organs (Lnn, Spleen, Malt).

Activated dendritic
cells from tissue
meet nave T cells
in T cells area of
secondary
lymphoid organs

Three signals are

needed to activate T
cells

APCs deliver three kinds of signals for the clonal expansion and
differentiation of naive T cells

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Multiple signaling pathways convergence on the IL-2 promoter

NFAT (Nuclear factor of activated T cell), AP-1 (transcription factor)& NF B

(transcription factor) is to act together to stimulate IL-2 transcription
proliferation & differentiation of T cells

22

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Antigen recognition in the absence of co-stimulation leads to

functional inactivation or clonal deletion of peripheral T cells

24

Various forms of signal 3 induce the differentiation of nave CD4 T cell to

several distinct types of effector function

25

Effector T cells enter blood circulation and migrate to

infected tissue
CD8+ cytotoxic
T cells

CD4+ helper
T cells

Infected tissue

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Activation signals
should be
stopped:

Negative feedback
of TCR signaling

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Developmental Phase

Activation and Action Phase

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Interfolliculer area
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