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Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4
K S Boles1, H Nakajima, M Colonna
1Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth 76107-2699, USA.
Abstract:
Natural killer (NK) cells spontaneously detect and kill cancerous and virally infected cells through receptors that transduce either activating or inhibiting signals. The majority of well studied NK receptors are involved in inhibitory signaling. However, we have previously described an activating receptor, 2B4, expressed on all murine NK cells and a subset of T cells that mediate non-major histocompatibility complex (MHC) restricted killing. Anti-2B4 monoclonal antibodies directed against IL-2-activated NK cells enhanced their destruction of tumor cells. Recently, we determined binding of 2B4 to CD48 with a much higher affinity than CD2 to CD48. Here we describe the molecular characterization of a cDNA clone homologous to mouse 2B4, isolated from a human NK cell library. The cDNA clone contained an open reading frame encoding a polypeptide chain of 365 amino acid residues. The predicted protein sequence showed 70% similarity to murine 2B4. Additionally, it has 48, 45, and 43% similarity to human CD84, CDw150 (SLAM), and CD48, respectively. RNA blot analysis indicates the presence of 3 kb and 5 kb transcripts in T- and NK-cell lines. A single transcript of 3 kb is identified in poly(A)+ RNA from human spleen, peripheral blood leukocytes, and lymph node, whereas, the level of expression in bone marrow and fetal liver was indeterminate. Preliminary functional data suggests that NK-cell interaction with target cells via 2B4 modulates human NK-cell cytolytic activity.
Insights
Researchers identified a human homolog of the mouse 2B4 activating receptor, crucial for natural killer (NK) cell cancer detection. This discovery advances understanding of immune cell interactions and cancer immunity.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Natural killer (NK) cells are vital for innate immunity, eliminating cancerous and virally infected cells.
- NK cell activity is regulated by activating and inhibitory receptors; inhibitory receptors are more extensively studied.
- The 2B4 molecule is a known activating receptor on murine NK and T cells mediating non-MHC restricted killing.
Purpose of the Study:
- To molecularly characterize a human homolog of the murine 2B4 activating receptor.
- To investigate the expression patterns of the human 2B4 homolog.
- To explore the functional role of human 2B4 in NK cell-mediated cytotoxicity.
Main Methods:
- Isolation and sequencing of a cDNA clone from a human NK cell library.
- Bioinformatic analysis to predict protein sequence and similarity to known receptors.
- RNA blot analysis to determine transcript expression in various human tissues and cell lines.
Main Results:
- A human cDNA clone homologous to mouse 2B4 was identified, encoding a 365-amino acid protein with 70% similarity to its murine counterpart.
- The human 2B4 homolog shares similarity with human CD84, SLAM, and CD48.
- Transcripts were detected in T-cell and NK-cell lines, spleen, peripheral blood leukocytes, and lymph node, with varying levels in bone marrow and fetal liver.
Conclusions:
- A human 2B4 homolog has been molecularly characterized.
- The human 2B4 receptor is expressed in immune cells and tissues relevant to immune responses.
- Preliminary data suggests 2B4 engagement modulates human NK cell cytotoxic activity, highlighting its potential role in immune regulation.
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