• Purity

  >95%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its binding ability in a functional ELISA. When Recombinant Human CD161 Fc Chimera is coated at 5 μg/mL (100 μL/well), the concentration of recombinant human CLEC-2A Fc Chimera that produces 50% optimal binding response is found to be approximately 2-10 μg/mL.

• Source

  Chinese Hamster Ovary cell line, CHO-derived

  Met-Asp	Human IgG1 (Pro100-Lys330)	IEGR	Human CD161 (Lys68-Ser225) Accession # Q12918
  N-terminus			C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Met-Asp

• Predicted Molecular Mass

  45 kDa

• SDS-PAGE

  58-70 kDa, reducing conditions

Background: CD161

CD161 (also NKR-P1A, CLEC5B and KLRB1) is a 40-44 kDa member of the NKR (Natural Killer cell receptor) family, C-type lectin superfamily of molecules (1-4). It is a cell surface protein that is known to be expressed by distinct sets of lymphocytes. These include DN immature thymocytes (4), NK17 (CCR4  ⁺; Np44  ⁺; IL-23 R  ^-) cells that secrete IL-17 (5), TCR alpha beta CD8 alpha   ⁺ intestinal T cells (6), TCR alpha beta NKT cells (7), TCR gamma δ T cells (8), Type-2 Innate (CD127  ⁺ CRTH2  ⁺) lymphoid cells that produce IL-5 and IL-13 (9), immature CD56  ^- CD16  ^- NK cells (10), CD56  ⁺ CD16  ⁺ and CD56  ⁺ CD16  ^- NK cells (3, 11, 12), and CD4  ⁺ Th17 plus CD8  ⁺ Tc17 IL-17 secreting T cells (13, 14). Although monocytes and dendritic cells have also been reported to express CD161, cells with antigen-presenting function are more often associated with expression of LLT1, the ligand for CD161 (15, 16). Human CD161 is a 225 amino acid (aa) type II transmembrane glycoprotein. It contains a 45 aa N-terminal cytoplasmic region, a 21 aa transmembrane segment, and a 159 aa extracellular domain (ECD) (aa 67-225) (3, 17). The ECD contains one C-type lectin domain (aa 101‑211) and, based on the mouse ortholog for human CD161, will utilize Cys74 for the creation of a disulfide-linked homodimer (3, 4). Full-length human CD161 shares 47% aa sequence identity with full-length mouse NK1.1/Ly55c, the closest mouse ortholog to human CD161. Within the ECD of these molecules, human CD161 shares 45% aa sequence identity with mouse NK1.1. The function of CD161 is not well understood. It is known to possess a weak ITIM motif (AIYAEL) in its cytoplasmic tail, and to utilize acid sphingomyelinase for signal transduction that results in the activation of PI3 kinase (18, 19). Unlike all the mouse orthologs for CD161, human CD161 does not possess a p56  ^lck motif; the significance of this, however, is unclear (19). CD161 is generally regarded as a marker for IL-17 secreting cells (8, 16, 20). Whether its expression is a requisite for IL-17 secretion is uncertain. What does appear certain is the fact that CD161 activity is a function of the expressing cell type. Although the data is somewhat conflicting, on T cells, CD161 reportedly acts as an activation/potentiation receptor, increasing IFN-gamma production in concert with TCR engagement (16, 18, 21). On NK cells, CD161 ligation decreases cell-mediated cytotoxicity and IFN-gamma production (11, 16, 21, 22, 23). And on thymocytes, CD161 activation induces proliferation and down‑regulates innate cytolytic activity (4). Finally, CD161 may also function through binding to LLT1/CLEC2D (note: PILAR/CLEC2A was also previously reported to bind to CD161, but this is now in dispute) (22-25). When LLT1 is expressed on NK cells, its engagement by CD161 actually induces IFN-gamma production by NK cells, in contrast to the down‑regulation effect seen with CD161 ligation.

• References:

1. Mesci, A. et al. (2006) Immunol. Res. 35:13.

2. Carlyle, J.R. et al. (2008) Semin. Immunol. 20:321.

3. Lanier, L.L. et al. (1994) J. Immunol. 153:2417.

4. Poggi, A. et al. (1996) Eur. J. Immunol. 26:1266.

5. Pandya, A.D. et al. (2011) PLos ONE 6:e26780.

6. Turtle, C.J. et al. (2011) Blood 118:2752.

7. Balato, A. et al. (2009) J. Invest. Dermatol. 129:1628.

8. Maggi, L. et al. (2010) Eur. J. Immunol. 40:2174.

9. Mjosberg, J.M. et al. (2011) Nat. Immunol. 12:1055.

10. Bennett, I.M. et al. (1996) J. Exp. Med. 184:1845.

11. Poggi, A. et al. (1998) Eur. J. Immunol. 28:1611.

12. Azzoni, L. et al. (1998) J. Immunol. 161:3493.

13. Annunziato, F. et al. (2008) Int, Immunol. 11:1361.

14. Billerbeck, E. et al. (2010) Proc. Natl. Acad. Sci. USA 107:3006.

15. Poggi, A. et al. (1997) Eur. J. Immunol. 27:2965.

16. Germain, C. et al. (2011) J. Biol. Chem. 286:37964.

17. SwissProt Accession # Q12918.

18. Rosen, D.B. et al. (2008) 180:6508.

19. Pozo, D. et al. (2006) J. Immunol. 176:2397.

20. Cosmi, L. et al. (2008) J. Exp. Med. 205:1903.

21. Kamishikiryo, J. et al. (2011) J. Biol. Chem. 286:23823.

22. Aldemir, H. et al. (2005) J. Immunol. 176:7791.

23. Rosen, D.B. et al. (2005) J. Immunol. 176:7796.

24. Huarte, E. et al. (2008) Blood 112:1259.

25. Germain, C. et al. (2010) J. Biol. Chem. 285:36207.

26. Bambard, N.D. et al. (2010) Scand. J. Immunol. 71:210.

• Entrez Gene IDs:

  3820 (Human)

• Alternate Names:

  CD161 antigen; CD161; CLEC5B; CLEC5BC-type lectin domain family 5 member B; HNKR-P1a; killer cell lectin-like receptor subfamily B member 1; killer cell lectin-like receptor subfamily B, member 1; KLRB1; Ly59; Natural killer cell surface protein P1A; NKR; NKRP1; NKR-P1; NKRP1A; NKR-P1AMGC138614; NKRP1ANKR