CD161, also known as KLRB1, is a protein found on the surface of various immune cells, playing a part in the body’s defense system. It is a type II transmembrane protein, spanning the cell membrane. This protein is present on both innate and adaptive immune cells, highlighting its broad involvement in immune responses. Its presence on these cells suggests a role in their communication and function.
Understanding CD161
CD161 is a C-type lectin-like receptor. It possesses a carbohydrate-recognition domain, though its primary function is not always direct sugar binding. The gene encoding CD161 (KLRB1) is located within the natural killer cell gene complex on chromosome 12.
This protein is predominantly found on the surface of several immune cell types. It is expressed on the majority of natural killer (NK) cells, which are lymphocytes responsible for early responses to infections and tumor cells. CD161 is also present on approximately a quarter of adult peripheral blood T cells, including both CD4+ T helper and CD8+ T cell subsets. These T cell populations are involved in specific, adaptive immune responses, such as coordinating other immune cells or directly killing infected cells. CD161 expression is also found on mucosal-associated invariant T (MAIT) cells, another type of innate-like T cell.
How CD161 Functions in the Immune System
CD161 acts as a co-signaling receptor, influencing T-cell receptor-dependent responses. Its interaction with its ligand, Lectin-like transcript 1 (LLT1), modulates immune cell activity. This interaction often inhibits NK cell-mediated cytotoxicity and interferon-gamma secretion in target cells.
However, the specific functional role of CD161 can be complex, particularly within different T cell subsets. For instance, CD161 is a marker for T helper 17 (Th17) cells, which produce interleukin-17 (IL-17). IL-17 is a cytokine involved in inflammatory responses and host defense against certain pathogens. CD161 expression on T cells is linked to an enhanced ability to produce various cytokines, including IL-17 and interferon-gamma (IFN-γ).
CD161’s Role in Health and Illness
CD161’s presence and activity are implicated in various health conditions, ranging from autoimmune disorders to infectious diseases and cancer. In autoimmune diseases like multiple sclerosis and rheumatoid arthritis, alterations in CD161 expression or function can contribute to the inflammatory processes. CD161+ T cells might play a part in the immune dysregulation observed in these conditions.
In infectious diseases, CD161 can influence the immune response to pathogens. Its role in cytokine production, such as IFN-γ, is relevant for antiviral immunity, as IFN-γ helps control viral replication. Conversely, in certain chronic infections like HIV and hepatitis, CD161 expression patterns on immune cells can shift, impacting the body’s ability to clear the infection.
CD161 is also investigated as a potential prognostic biomarker and immunotherapy target in various cancers. Differential expression of CD161 has been observed between cancerous and normal tissues in many cancer types. Higher CD161 expression is associated with poorer overall survival in some cancers, such as brain lower-grade gliomas and uveal melanoma. This suggests CD161’s involvement in regulating immune processes within the tumor microenvironment, potentially contributing to immune suppression that allows cancer to progress.