Chronic lymphocytic leukaemia (CLL) is a slow-growing leukaemia that affects developing B-lymphocytes (B-cells). Under normal conditions B-cells produce antibodies that help protect our bodies against infection and disease. Lymphocytes in CLL patients undergo a malignant change and become leukaemic cells. Previous studies have identified defects in immune lineages of patients with CLL, but their significance to the development, progression and treatment of CLL is poorly understood.
Mucosal-associated invariant T (MAIT) cells recognise vitamin B related antigens presented by MR1, an MHC class I-related antigen-presenting molecule. Upon recognition of vitamin B metabolites on MR1, MAIT cells become activated and rapidly produce cytokines. Activated MAIT cells have potent antimicrobial functions and the ability to induce dendritic cell and monocyte maturation, as well as NK cell transactivation. Preliminary studies in patients with CLL have identified altered populations of MAIT cells. The function of MAIT cells and related T cells in CLL patients will be investigated, including the nature and impact of their functional response to CLL cells and their value as potential targets as new immunotherapies. The interactions between MAIT cells and other cell types, including CLL cells will be investigated. This will include cellular and molecular analysis of MAIT cells and other immune cells from CLL patients and from healthy donors. The overarching goal is to develop new knowledge about the interactions between the immune system and CLL which may lead to improved treatments.