NKT cells are innate T cell lineage.

1. Darshan S

2. Contents
• Introduction
• Ontogeny and markers
• TCR
• Ligands
• CD1d loading
• Activation of immune cells
• Adjuvant use
• Role in diseases
• Reference

3. Introduction
• Unconventional T cells
• Antigens presented on CD1d
• Rapid cytokine production
• mVα14 ~0.5% T cell population in blood and peripheral
lymph nodes
• ~2.5%- spleen, mesenteric and pancreatic lymph nodes
• ~0.5% in thymus

4. Introduction
1987 1992 1994 1995 1997
Ralph Budd and
collaborators
described
immature DN cells
BJ Fowlkes and
colleagues at NIH
described lymphocyte
population that shared
characteristics of T &
NK cells
Hasashi et al.
described NKT
population with
NK1.1 awa TCR
Oliver and
Bendelac at NIH
demonstrated
invariant α chains
in NKT TCRs
Bendelac et al.
showed NKTs
recognize CD1
Kawana et al.
KRN7000

5. Ontogeny
*Roitt’s Essential immunology, Wiley Blackwell

6. *Bendelac, A., Savage, P.
B. & Teyton, L. The
biology
of NKT cells. Annu. Rev.
Immunol.

7. Markers
• T cells CD3+ CD56-
• NK cells CD3- CD56+
• NKT cells CD3+ CD56+

8. TCR
• Type I (iNKTs) have invariant TCRα-chain
• Type II have diverse TCRs
• Vα14-Jα18 α chain with a variable Vβ8,-7, or -
2 β chain in mouse or Vα24-Jα18/Vβ11 in
human
• Vα3.2-Jα9/Vβ8, Vα8/Vβ8

9. *Roitt’s Essential immunology, Wiley Blackwell

10. Ligands

12. Microbial ligands
*Bendelac, The biology of NKT cells
• Sphingomonas
• Borrelia
burgdorferi
• PIM-4

13. iGb3

14. CD1d loading
*Bendelac, The biology of NKT cells

15. *Bendelac, The biology of NKT cells

16. Activation of immune cells
*Dale Godfrey, Berzins, SP, Control points in NKT cell development, Nature. Rev.
Immunol.

17. Adjuvant use
• Malaria, HIV, TB
• Immunogenicity and protective efficacy

18. HIV
• BCG vector – priming
• Ad vector – boosting
• SIV-gag antigen
• Overcoming kinetic mismatch b/w virus
replication and generation of effective
immune control

19. Malaria
• Ad vectors
• Ag of different sporzoite stages (eg. PfCSP) or
apical membrane Ag (PfAMA1) of Plasmodium
falciparum
• Early activation of DCs followed by CD8+
response

20. Influenza
• 7DW8-5 increases vaccine efficacy of HA split
vaccine (targeted to elderly)
• Both TH1 & TH2 type response is seen
• T cell targeting broadens cross reactivity

21. Role in diseases
Characterized by
• Antimitochondrial antibodies
• Liver lymphocytic infiltrates
• Chronic destruction of the biliary epithelium
Primary Biliary Cirrhosis

22. Asthma
• Bronchial TH2 infiltrates
• IgE antibodies
• Decreased allergen induced airway
hyperreactivity in the alumovalbumin model
(in CD1d- and Jα18-deficient mice) of asthma

23. Cancer
• Both tumor rejection and suppression of
rejection have been observed
• Myelomonocytic and cells of B cell origin bear
CD1d – NKT cell-mediated cytotoxicity
• Downregulation of CD1d in HPV cervical
carcinoma

24. Reference
• Ivan M Roitt, Roitt’s Essential Immunology,2011, Thirteenth edition,
Wiley Blackwel
• Albert Bendelac, Paul B. Savage, Luc Teyton, The Biology of NKT
Cells, Annual Review of Immunology 2007 25:1, 297-336
• Kawano et. al CDl d-Restricted and TCR-Mediated Activation
• of Val 4 NKT Cells by Glycosylceramides, 1997 science
• Rossjohn J et. al Nat Rev Immunol. 2012;12(12).
doi:10.1038/nri3328
• Opasawatchai, Anunya & Matangkasombut, Ponpan. (2015). iNKT
Cells and Their Potential Lipid Ligands during Viral Infection.
Frontiers in immunology. 6. 378. 10.3389/fimmu.2015.00378.

25. • Manjunatha M. Venkataswamy,
Improving Mycobacterium bovis Bacillus
Calmette-Guèrin as a Vaccine Delivery Vector
for Viral Antigens by Incorporation of
Glycolipid Activators of NKT Cells, 2014 Plos
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