1. 1. Surface markers on T lymphocytes
and their function
2. Subsets of T lymphocytes
3. Function of T lymphocytes
T lymphocytes
2. T cells are composed of a group of functionally
different and heterogeneous lymphocytes. They
are so called because they differentiate and
mature in thymus.
Mature T cells emigrate thymus and reside ： in
paracortical area of lymph node and around small
arteries of spleen white pulp ： in peripheral
lymphoid tissue.
T cells execute specific cellular immune response
and play an important role in TD-Ag induced
humoral immune response.
3. Part I T cell differentiation and development
Thymic microenviroment
Differentiation course of T cells
Selection of T cells in thymus----
positive selection and negative
selection
14. 3.Differentiation of T cells in
thymus
Changes in thymus ：
• TCR rearrangement ----functional TCR
• Positive selection and negative selection
T cells acquire MHC restriction and Self
tolerance
15.
16. Positive selection
• DP cells whose TCRs
recognize and combine with
MHC molecules can
differentiate and develop
continuously----SP
• DP cells whose TCRs can’t
recognize with MHC
molecules or bind with high
affinity go apoptosis
17. Positive Selection
• Results in MHC restriction
• Mechanism:
– Immature thymocytes cluster with MHC
molecules on the cortical cells of the thymus
• If TCR interacts with MHC protective signal
results that prevents apoptosis.
• If TCR does not interact with MHC no protective
signal and apoptosis occurs.
• Only reactive thymocytes survive.
18. Negative seletion
• cells whose TCRs can’t recognize with
self antigen peptide develop and
differentiate continuously
• SP cells whose TCRs recognize and
combine with self antigen peptide tightly
go apoptosis or become clonal anergy
• Acquired self tolerance
25. TCR complex
Definition: A group of
membrane molecules on
T cells that can specially
bind to the antigen and
pass activation signal into
T cells, consisting of TCR
(αβ or γδ), CD3(γε,δε, ζ ζ)
++ −− −−
γδ
βαTCR
ζζ
ε ε
CD3CD3
26. 1. TCR
(1)Definition: A kind of membrane
molecules on T cells that can specially bind
to the antigenic peptide-MHC molecule
complex
(2)Types ： αβTCR
γδTCR
27. (3) Structure of TCR(3) Structure of TCR
Extracellular region:Extracellular region:
V region: VV region: V αα and Vand V ββ
antigen binding siteantigen binding site
C region: CC region: Cαα and Cand Cββ
Transmembrane region:Transmembrane region:
anchoring domainanchoring domain
positive chargepositive charge
Cytoplasmic region:Cytoplasmic region:
cancan’’t transduce signalt transduce signal
（ 3~12aa ）
+ +
28. 2 CD3
Consists of γε,δε, ζζ
Important membrane molecules of T cells
Pass activation signal into T cells
Contain ITAM in the cytoplasmic region
29. ITAM (Immunoreceptor tyrosine-
based activation motif) :
• ITAM is a conserved motif composed of two
copies of the sequence tyrosine-X-X-leucine
found in the cytoplasmic tails of various
membrane proteins that are involved in signal
transduction.
• When these receptors bind their ligand, the
tyrosine residues of the ITAMs will be
phosphorylated by the receptor associated
tyrosine kinases in order to transmit
activation signal.
31. 2. T cell accessory molecules
Accessory molecules-----related to the
32. Part T cell accessory moleculesⅡ
1. CD4 and CD8: co-receptor
CD4----class MHCⅡ
Receptor of HIV
CD8----class Ⅰ MHC
33. CD8 binds MHC class I
CD4 binds MHC class II
Most mature T cells are either CD4+ or CD8+.
CD8 T cells kill cells infected with intracellular pathogens or tumor cells
while CD4 T cells regulate (activate or suppress) other immune cells’ function (e.g.B cells and
mac).
34. To bind p56lck tyrosine-protein kinase ,involve in the signal
transduction that leads to T cell activation and proliferation
LCK
35. 2. Co-stimulatory receptor: CD28
CD28 on resting or activated T cells binds
to the B7(CD80/CD86) on APC
Contain ITAM domain
Transduct an important co-stimulatory
signal to T cells
37. 3. CTLA-4
CTLA-4(cytotoxic T lymphocyte antigen-4,
CD152) on activated T cells binds to B7
on APC
Homologous to CD28
Bind to B7 with high affinity
Contain ITIM domain
Transmit an inhibitory signal to T cells
Part T cell accessory moleculesⅡ
38. T cell Antigen presenting cell
CTLA4 – a CD28 homologue that
binds to B7 with higher affinity than CD28
TCR
B7
MHC + peptide
CD28
CTLA4
ITIM
39. 4. CD2(LFA-2, Sheep red blood cell
receptor)
Expressed on 90% mature T cells( none on B cells)
Its ligand is CD58(LFA-3) expressed on APC, RBC
of human or sheep
Functions:
------Enhance the binding of TCR and antigenic
peptide-MHC molecule complex
------Participate in signal transduction of T cell
activation
40. 5. LFA-1(lymphocyte function antigen-1)
• CD11a/CD18
• Its ligand is ICAM-1(CD54),2,3
• Mediated adhesion between T cell and APC or
target cell
6. VLA-4(very late antigen-4)
• CD49d/CD29
• Its ligand is VCAM-1,fibronectin,laminin
• Mediated adhesion between T cell and APC or
target cell
Part T cell accessory moleculesⅡ
41. 7. Mitogen receptor:
---Related to lymphocyte transformation test
PHA, ConA
---Activating T cell only
PWM
---Activating T and B cells
8. Cytokine receptor: IL-2R,IL-12R
Part T cell accessory moleculesⅡ
42. The major surface molecules of CD4+ T cells involved in the
activation of these cells (the receptors) and the molecules
onAPCs (the ligands) recognized by the receptors are
shown. CD8+ T cells usemost of the same molecules,
except that the TCR recognizes peptide–classI MHC
complexes, and the coreceptoris CD8, which recognizes
class IMHC.
44. 1. According to activating stage of T cells
Naïve T cell
Activated T cell
Effective T cell
Memory T cell
45. Naïve T cell Memory T cell
Stimulation of Ag no yes
IL-2R(high avidity) no yes
CD45 CD45RA CD45RO
MHC-Ⅱ molecule no yes
ICAM no yes
46. 2.To divide into αβT 、 γδT subsets according to
TCR type
In peripheral blood ,αβT cells account for 95%
while γδT cells range from 1% to 10% 。 The
two subsets of T cells have different
characteristics and functions. αβT cells are the
main T cells participating in immune response.
48. TCRαβTCD4+ cells: TCR antigen recognition is MHC restrictive.Ⅱ
TCRαβTCD8+ cells:TCR antigen recognition is MHC I restrictive.
3. To divide to CD4+ T cells or CD8+ T cells
according to whether T cells express CD4 or
CD8
50. Master the types and structure of TCR
Master T subset categories and the
biological features of different subsets
Master the developmental process of T cells
Familiarize the main membrane molecules
on T cell surface and their function
Understand the similarity and differnce
between TCRγδT cells and TCRαβT cells
