Browsing by Subject "2b4"
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Item Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)(MDPI, 2023-02-26) Powers, Sheila B.; Ahmed, Nourhan G.; Jose, Roslin; Brezgiel, Marissa; Aryal, Subhash; Bowman, W. Paul; Mathew, Porunelloor A.; Mathew, Stephen O.Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interaction with their ligands. In this study, the expression of 2B4, CS1, LLT1, NKp30 and NKp46 was determined. The expression profiles of these immune receptors were analyzed in the peripheral blood mononuclear cells of B-ALL and T-ALL subjects by single-cell RNA sequencing data obtained from the St. Jude PeCan data portal that showed increased expression of LLT1 in B-ALL and T-ALL subjects. Whole blood was collected from 42 pediatric ALL subjects at diagnosis and post-induction chemotherapy and 20 healthy subjects, and expression was determined at the mRNA and cell surface protein level. A significant increase in cell surface LLT1 expression in T cells, monocytes and NK cells was observed. Increased expression of CS1 and NKp46 was observed on monocytes of ALL subjects at diagnosis. A decrease of LLT1, 2B4, CS1 and NKp46 on T cells of ALL subjects was also observed post-induction chemotherapy. Furthermore, mRNA data showed altered expression of receptors in ALL subjects pre- and post-induction chemotherapy treatment. The results indicate that the differential expression of the receptors/ligand may play a role in the T-cell- and NK-cell-mediated immune surveillance of pediatric ALL.Item Functional Role of 2B4+ CD8+ T Cells Against HIV Epitopes(2009-07-01) Aldy, Kim N; Mathew, StephenAcquired immune deficiency syndrome (AIDS), caused by Human Immunodeficiency Virus (HIV) is the most devastating global health problem. Long Term Non Progressors (LTNP) are seropositive individuals that have delayed progression to AIDS. Potent anti-HIV CD8+ T cell responses are associated with LTNP’s; therefore, an effective cytotoxic T cell (CTL) response is vital for the immune system to control HIV. Human leukocyte antigen (HLA) B14 and HLA B27 types are commonly present in LTNP’s. 2B4 (CD244) is expressed on NK cells, monocytes, basophils, eosinophils, and a small population of CD8+ T cells. Although the expression of 2B4+CD8+ T cells has been shown to increase during HIV disease progression, the role of 2B4+ CD8+ T cells has not been established. Studying the differences in activation and cytotoxic activity of 2B4+ and 2B4¯ CD8+ T cells will expand our knowledge of this receptor in T cells, which has not been fully addressed in the past. HIV infected patients could benefit from immunotherapy efforts using the knowledge we gain from 2B4 studies in T cells. In addition, the information gathered from this study can be used for in vivo studies of this receptor in natural HIV infection. The immunomodulatory effects of Corticotrophin releasing hormone and Epinephrine on 2B4- and 2B4+ CD8+ T cells during activation and the effects on cytotoxicity have not been published to date. Knowledge about their effects will allow us to learn the function of these hormones that are released due to stress during immune regulation in HIV disease.Item Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer(MDPI, 2020-07-01) Buller, Casey W.; Mathew, Porunelloor A.; Mathew, Stephen O.Natural killer (NK) cells play a pivotal role in the immune system, especially in the recognition and clearance of cancer cells and infected cells. Their effector function is controlled by a delicate balance between the activating and inhibitory signals. We have identified 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) as NK cell receptors regulating NK cell cytotoxicity. Lectin-like transcript 1 (LLT1), a member of the C-type lectin-like domain family 2 (CLEC2D), induced IFN-g production but did not directly regulate cytolytic activity. Interestingly, LLT1 expressed on other cells acts as a ligand for an NK cell inhibitory receptor NKRP1A (CD161) and inhibits NK cytolytic function. Extensive research has been done on novel therapies that target these receptors to increase the effector function of NK cells. The 2B4 receptor is involved in the rejection of melanoma cells in mice. Empliciti, an FDA-approved monoclonal antibody, explicitly targets the CS1 receptor and enhances the NK cell cytotoxicity against multiple myeloma cells. Our studies revealed that LLT1 is expressed on prostate cancer and triple-negative breast cancer cells and allows them to evade NK-cell-mediated killing. In this review, we describe NK cell receptors 2B4, CS1, and LLT1 and their potential in targeting cancer cells for NK-cell-mediated immunotherapy. New cancer immunotherapies like chimeric antigen receptor T (CAR-T) and NK (CAR-NK) cells are showing great promise in the treatment of cancer, and CAR cells specific to these receptors would be an attractive therapeutic option.