NKT & Gamma delta T cells

What antigen ppt does NKT cells recognise

A tumour cell contains abnormal lipids

1. The lipid (NOT PEPTIDE) is captured and presented by CD1d on a tumour cell's surface.

2. The NKT cell's TCR recognises the lipid–CD1d complex.

3. The NKT cell becomes activated.

4. It release cytokines, such as IFN-γ, and kill target cells.

What are γδ T cells? What antigen ppt do they recognise

γδ T cells have a TCR made of a γ (gamma) chain and a δ (delta) chain (instead of alpha and beta like conventional t cells)

γδ T cells can recognise certain signs of cellular stress or abnormal metabolism without requiring classical peptide–MHC presentation.

functions of NKT

T-cell characteristics

• Express a T-cell receptor (TCR).

• Recognise antigens through a receptor-dependent mechanism.

• Can produce cytokines and regulate other immune responses.

NK-cell-like characteristics

• Can respond rapidly.

• Can exhibit direct cytotoxicity.

• Can produce inflammatory cytokines such as IFN-γ.

How can α-GalCer be used in NKT based antitumour immunity- direct and indirect

α-GalCer is a glycolipid and binds to CD1D to produce NKT mediated killing

Direct killing of CD1d-positive tumour cells, and indirect killing through activation of other immune cells and modulation of the tumour microenvironment.

How do type 1 and type 2 NKT cells differ in cancer immunity?

TYPE 1 Can promote tumour killing

TYPE 2 Can suppress antitumour immunity

NKT cell based therapeutic stategies

A. Lipid agonist-based strategies- α-GalCer

B. Adoptive NKT-cell therapy (can also do a CAR-NKT cell therapy)

C. Bispecific NKT-cell engagers- These molecules bring NKT cells into contact with tumour-associated antigens, promoting targeted immune-cell activation.

D. 2. CD1d-specific single-domain antibodies- These antibodies bind CD1d and can stabilise the interaction between CD1d and the invariant NKT-cell TCR, enhancing NKT activation. Dual effect- It can promote type 1 NKT-cell activation while blocking CD1d-dependent activation of suppressive type 2 NKT cells.

Why are γδ2 T cells considered promising for antitumour immunotherapy?

Direct tumour killing,

inflammatory cytokine production

antigen presentation to support adaptive immunity.

Enhancing γδ T-cell immunotherapy- methods

Adoptive cell transfer

Amino bisphophonates/phosphoantigen + IL2

Bispecific antibody

BTN3A specific antibody

CAR

What are phosphoantigens, and why do they matter for Vγ9Vδ2 T cells?

They are phosphorylated metabolites that can accumulate in tumour or infected cells and trigger Vγ9Vδ2 T-cell activation through the butyrophilin recognition system.

• Endogenous phosphoantigens: generated by the body's own cells through metabolic pathways.

• Microbial phosphoantigens: produced by bacteria and other microbes.