Quentin Sattentau

Lymphocyte function in health and disease

The immune system protects us from infection and in some cases cancer. Lymphocytes comprise what is known as the adaptive arm of the immune system, and function to recognise and eliminate infectious and other threats. B lymphocytes (B cells) produce antibodies that bind invading pathogens and cancer cells and eliminate them, whereas T lymphocytes (T cells) can assist B (and other immune) cells and kill pathogen-infected and cancer cells.

Antibodies are considered to be the major protective immune response elicited by vaccination, and so the study of B cell responses to pathogens and their components is essential to produce the vaccines of the future. This is particularly true of difficult pathogens such as the human immunodeficiency virus type-1 (HIV-1) and cancers against which antibodies may help to protect us. Antibodies conventionally recognise protein targets, but can also engage carbohydrate (glycan) targets on viruses and cancer cells. Since immune escape by pathogens and cancers may be difficult when glycans are targeted, it is of interest to understand how B cells interact with glycans and produce glycan-specific antibodies. We have established systems for isolating single glycan-specific B cells and synthesising and analysing the monoclonal antibodies produced (Figure 1). In this way we are increasing our understanding of antibody-glycan interactions at the cellular, biophysical and structural levels which will guide future anti-pathogen and anti-cancer vaccine efforts.

T cells are central to immune system function, and expand dramatically in number in response to threats. Following this expansion and having carried out their role, the cells need to be rapidly cleared, and undergo a type of cell death called apoptosis. Apoptosis is a homeostatic form of cell death designed not to trigger inflammation. However, if apoptotic cells are not rapidly cleared they become necrotic, which is a highly inflammatory type of cell death and can lead to widespread inflammatory conditions. Thus, understanding mechanistically how apoptotic T cells are cleared is important to avoid and treat such inflammation-related diseases. We have established model systems for investigating clearance of dying T cells by scavenging cells called macrophages, and have studied molecular events taking place at the T cell membrane during apoptosis. We have identified a set of molecules called mucins that provide a protective barrier on the surface of the T cell under healthy conditions but which are shed by a membrane protease during apoptotic cell death to allow clearance by macrophages (Figure 2). These findings will help us to understand how we might modulate cell surface molecules during cell death to avoid inflammatory disease outcomes.

Selected Publications