CD161 at a glance

CD161, also known as Nkrp1 (natural killer receptor protein 1) or Klrb1 (killer cell lectin-like receptor subfamily b member 1), is a disulphide-linked homodimeric receptor, which is involved in regulation of NK cell and NKT cell function. Upon binding its ligand LLT1 (CLEC2D), CD161 inhibits their cytotoxicity and interferon gamma secretion.  Similarly, antibody-based triggering of CD161 can reduce cytotoxicity against target cells. On the other hand, CD161 serves also as a costimulatory T cell receptor. CD4+CD161+ and CD8+CD161+ cells can produce more proinflammatory cytokines compared to CD161-cells. These T cell populations include e.g. Th17 cells and memory T cells.

Whether coinhibitory or costimulatory function of CD161 in T cells takes part, it depends on other interactions.

 

 
Fig. 1: Whereas NK cell functions are upon CD161 triggering inhibited, analogous interaction in T cells can have either inhibitory or activatory effect, which is not only based on the T cell type, but also depends on the signaling context.
 
 
 
 
 
CD161 is upregulated during T cell homing into tissues. Importantly, this happens also in tumor-infiltrating T cells, that are there inhibited by interaction with LLT1 (CLEC2D), which is widely expressed in many cancer types. This phenomenon is interesting concerning possible cancer therapy. CD161 examining is relevant also in other illnesses, e.g. during viral infections, where CD161 positive NK cells contribute to inflammation-related pathogenesis.  
 
CD161 seems to represent one of key regulatory molecules with immunotherapeutic potential, and it is also a promising biomarker. However, due to complexity of its interactions, there is still a long way ahead to elucidate fully its roles in the immune system.
 
 
 
The mouse monoclonal antibody HP-3G10 recognizes an extracellular epitope of human CD161, and can be used for flow cytometry, Western blotting, and immunohistochemistry. Currently available formats:  Purified (11-729-C100), Alexa Fluor® 488 (A4-729-T100), PE (1P-729-T100), APC (1A-729-T100), Alexa Fluor® 647 (A6-729-T100), Alexa Fluor® 700 (A7-729-T100), PE-Cy™7 (T7-729-T100), APC-Cy™7 (T4-729-T100).
 

 
Fig. 2: Flow cytometry multicolor surface staining pattern of human lymphocytes stained using anti-human CD161 (HP-3G10) Alexa Fluor® 488 antibody (4 μl reagent / 100 μl of peripheral whole blood) and anti-human CD4 (MEM-241) Pacific Blue™ antibody (4 μl reagent / 100 μl of peripheral whole blood).
 
 
The mouse monoclonal antibody 10/78 recognizes a common extracellular epitope on rat CD161a and b isoforms, and can be used for flow cytometry, Western blotting, immunoprecipitation, immunohistochemistry and RIA. Currently available formats: Purified (11-657-C100), FITC (1F-657-C100), PE (1P-657-C100).
 

 
Fig. 3: Flow cytometry surface staining pattern of rat splenocytes stained using anti-rat CD161 (10/78) FITC antibody (concentration in sample 1 μg/ml).
 
 
 
Further reading:
 
Kurioka A et al.: CD161 defines a functionally distinct subset of pro-inflammatory natural killer cells: Front Immunol. 2018 Apr 9:9:486.
 
Wyrożemski Ł and Qiao SW: Immunobiology and conflicting roles of the human CD161 receptor in T cells. Scand J Immunol. 2021 Sep;94(3):e13090.
 
Ye W et al.: CD161, a promising immune checkpoint, correlates with patient prognosis: A pan-cancer analysis. J Cancer. 2021 Sep 9;12(21):6588-6599.
 
Mathewson ND et al.: Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell. 2021 Mar 4;184(5):1281-1298.e26.
 
Duurland CL et al.: CD161 expression and regulation defines rapidly responding effector CD4+ T cells associated with improved survival in HPV16-associated tumors. J Immunother Cancer. 2022 Jan;10(1):e003995.
 
Karunathilaka A et al.: CD161 expression defines new human γδ T cell subsets. Immun Ageing. 2022 Feb 22;19(1):11.
 
Alvarez-Calderon F et al.: Targeting of the CD161 inhibitory receptor enhances T-cell-mediated immunity against hematological malignancies. Blood. 2024 Mar 21;143(12):1124-1138.