CYTOTOXIC T-CELL AND THEIR MECHANISM OF

ACTION

Course –SOS In Biotechnology

Semester- M.Sc II sem

Paper- BT-202 (Immunotechnology)

Unit-IV

Topic- Cytotoxic T-cell and their mechanism of

action

By – Dr. Preeti Gupta

INTRODUCTION

Cytotoxic T-lymphocytes or CTLs are generated by immune

activation of T cytotoxic (Tc) cells.

These effector cells are CD8+ , MHC I restricted and have

lytic capability.

These cells are critical in recognition and elimination of

altered self cells (e.g., virus infected cells, tumor cells)

Effector molecules produced by CTLs are of two types –

membrane bound effectors- e.g., Fas ligand (FAS)

Soluble effectors- e.g., cytotoxins (perforins and

granzymes)

TYPES OF EFFECTOR T-CELL

Helper T-cell (CD4+) Cytotoxic T-cell (CD8+)

TH 1 TH 2 CTL

MHC II restrictedMHC I restricted

Involve in direct

killing of target cell Helps in the activation

of other immune cells

by releasing cytokines

CTL Mediated Immune Response

or their mechanism of action

I phase II phase

Activates and differentiates

naïve Tc cells into functional

effector CTLs

Effector CTLs recognise

antigen –class I MHC

complexes on specific cells,

which leads them to destroy

the target cell

I phase- Generation of CTLs

Naïve Tc cells are incapable of killing target cell , hence referred as CTL

precursor (CTL-Ps)

Once naïve Tc (CTL-Ps) activated , it will differentiate into functional CTLs

with cytotoxic activity.

Generation of CTLs from CTL-Ps requires at least three signals

1. An antigen specific signal -1 transmitted by TCR complex upon

recognition of a peptide-class I MHC mol complex.

2. A co-stimulatory signal transmitted by the CD28-B7interaction of the

CTL-Ps and the APC.

3. A signal induced by the interaction of IL-2 with the high affinity IL-2

receptor, resulting in proliferation and differentiation of the antigen

activated CTL-P into effector CTL.

Generation of effector CTLs

II phase- Destruction of target cells by CTLs

Two mechanisms that are responsible for initiating CTLs

mediated destruction of target cells:

1. Perforin –granzyme mediated cell killing- Directional delivery

of cytotoxic proteins (perforin and granzymes) released from

CTLs and enter target cells.

2. Fas/FasL-mediated cell killing- Interaction of membrane

bound Fas ligand on CTLs with the Fas receptor on the

surface of target cell

Perforin- granzyme mediated cell killing

Recognition of specific target cell bearing antigen +

class I MHC by CTL

Formation of CTL/target cell conjugates

Reorientation of cytoplasmic granules within the CTL

towards the region of contact with the target cell

Release of granular content within the zone of

cellular adhesion

Formation of pores in target cell

membrane

Dissociation of CTL from target cell and

subsequent destruction of target cell by

apoptosis

Fas/FasL- mediated cell killing

Interaction/ crosslinking of Fas ligand of

CTL with Fas of target cell

Activate caspase 8

Fas present on target cell is associated with protein known

as FADD (Fas associated protein with death domain) which

in turn associates with procaspase 8

Initiating apoptotic caspase cascade

Lysis of target cell by apoptosis

Thanks