Antigens: Lipids
Authors: Matsuda Kazuhiro 
Published: April 2013

Molecular mechanisms of lipid‐antigen recognition are important in the frontier of immunology. Possible pathogeneses of autoimmune diseases and tumours now include infections with microorganisms. Therefore, the role of vaccines is increasingly important, as advancing technology has now broadened the targets of vaccination to include a greater number of infectious diseases, tumours, chronic infections, autoimmune diseases and allergies. To prevent infectious diseases through vaccination, it is important to identify specific antigens, which often exist in the cell membrane and capsule and also become the centre of host–pathogen interactions. Structural analysis of lipid‐antigens is critical for understanding the mechanisms of molecular interactions involved in the pathogenesis of immune abnormalities, and for devising strategies surrounding immune system regulation and drug discovery.

Key Concepts:

Until recently, it had been the paradigm that T cells recognise peptide antigens that are presented by major histocompatibility complex (MHC) class I or II molecules. It has now been demonstrated that lipids can be presented by antigen‐presenting cells (APC) through the CD1 family of molecules. The structures of the CD1 family of molecules are similar to those of MHC class I and II molecules.

It is now recognised that continued immunological stimulus by chronic or repetitive infections with microorganisms can result in disease mechanisms that are seen in autoimmune diseases and tumours.

Glycolipids and phospholipids are major components of biomembranes (lipid bilayers) in which hydrophobic tail groups aggregate and form micelles with head groups facing towards the outside membrane. Glycolipids and phospholipids play important roles in intracellular vesicular trafficking; for example, in the endoplasmic reticulum.

Some human diseases are caused by antiphospholipid antibodies (antiphospholipid syndrome) and by antiglycolipid antibodies (antiglycolipid syndrome).

Microbial cell walls, which contain glycolipids and phospholipids, are rich in antigens. Such antigens are located on the surface of the microbial cell membranes and are therefore important in the host recognition of microbial infections and subsequent immune responses in higher organisms.

Although there are exceptions to these generalisations, Gram‐negative bacteria contain lipopolysaccharide (LPS) anchored by lipid A, Gram‐positive bacteria contain lipoteichoic acid (LTA) structures consisting mainly of glycerolipids, mycobacteria contain lipoarabinomannan (LAM), and mammalian cells contain glycerolipids and sphingolipids.

Autoreactivity is much more common than autoimmune disease and does not always results in illness. Autoimmune diseases can best be understood as being a result of multistep processes with a loss of self‐tolerance. Autoimmune diseases require development of autoreactivity as well as initiation of effector mechanisms.

Since mycoplasmas are contained only by a plasma membrane, it has been thought that lipid antigens in the cell membrane play an important role in the immune response against them. Mycoplasma lipid‐antigens (mycoplasma‐mimic particles) present carbohydrates as specific antigens for antibody‐mediated humoral immunity and present lipid‐antigen‐specific characters for cellular immunity.

Key lipid‐antigens and their structures can be used to understand the mechanisms of molecular interactions and pathogenesis of immune abnormalities, and can be used to devise strategies for immune system regulation and drug discovery.

The role of vaccines is increasingly important in medicine because advancing technology has broadened the targets of vaccination to include a greater number of infectious diseases, autoimmune diseases, tumours, chronic infections and allergies.