Antigens: Lipids


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.

Keywords: vaccine; antigen presentation; CD1; phospholipid; glycolipid; lipopolysaccharide; lipid A; lipoteichoic acid; lipoarabinomannan; mycoplasma lipid‐antigen

Figure 1.

Structures of mammalian lipids.

Figure 2.

Structures of microbial lipids.



Alviar CL, Echeverri JG, Jaramillo NI et al. (2011) Infectious atherosclerosis: is the hypothesis still alive? A clinically based approach to the dilemma. Medical Hypotheses 76: 517–521.

Ang CW, Tio‐Gillen AP, Groen J et al. (2002) Cross‐reactive anti‐galactocerebroside antibodies and Mycoplasma pneumoniae infections in Guillain–Barré syndrome. Journal of Neuroimmunology 130: 179–183.

Atkinson TP, Duffy LB, Pendley D, Dai Y and Cassell GH (2009) Deficient immune response to Mycoplasma pneumoniae in childhood asthma. Allergy and Asthma Proceedings 30: 158–165.

Blank M, Asherson RA, Cervera R and Shoenfeld Y (2004) Antiphospholipid syndrome infectious origin. Journal of ClinicalImmunology 24: 12–23.

Boonyarattanakalin S, Liu X, Michieletti M, Lepenies B and Seeberger PH (2008) Chemical synthesis of all phosphatidylinositol mannoside (PIM) glycans from Mycobacterium tuberculosis. Journal of the American Chemical Society 130: 16791–16799.

Borg NA, Wun KS, Kjer‐Nielsen L et al. (2007) CD1d‐lipid‐antigen recognition by the semi‐invariant NKT T‐cell receptor. Nature 448: 44–49.

Braud VM, Allan DS and McMichael AJ (1999) Functions of nonclassical MHC and non‐MHC‐encoded class I molecules. Current Opinion in Immunology 11: 100–108.

Bricard G and Porcelli SA (2007) Antigen presentation by CD1 molecules and the generation of lipid‐specific T cell immunity. Cell and Molecular Life Sciences 64: 1824–1840.

Brigl M and Brenner MB (2004) CD1: antigen presentation and T cell function. Annual Review of Immunology 22: 817–890.

Chatterjee D and Khoo KH (1998) Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects. Glycobiology 8: 113–120.

Cohen NR, Garg S and Brenner MB (2009) Antigen presentation by CD1 lipids, T Cells, and NKT cells in microbial immunity. Advanced Immunology 102: 1–94.

Ekdahl KN, Bengtsson AA, Andersson J et al. (2004) Thrombotic disease in systemic lupus erythematosus is associated with a maintained systemic platelet activation. British Journal of Haematology 125: 74–78.

Esmon CT (2005) The interactions between inflammation and coagulation. British Journal of Haematology 131: 417–430.

Fujiwara M, Ishida N, Asano K et al. (2010) Variation of genes encoding GGPLs syntheses among Mycoplasma fermentans strains. Journal of Veterinary Medical Science 72: 805–808.

Gil C, Rivera A, Bañuelos D et al. (2009) Presence of Mycoplasma fermentans in the bloodstream of Mexican patients with rheumatoid arthritis and IgM and IgG antibodies against whole microorganism. BMC Musculoskeletal Disorders 10: 97–103.

Gründling A and Schneewind O (2007) Synthesis of glycerol phosphate lipoteichoic acid in Staphylococcus aureus. Proceedings of the National Academy of Sciences of the USA 104: 8478–8483.

Guerin ME, Korduláková J, Alzari PM, Brennan PJ and Jackson M (2010) Molecular basis of phosphatidyl‐myo‐inositol mannoside biosynthesis and regulation in mycobacteria. Journal of Biological Chemistry 285: 33577–33583.

Haggerty CL (2008) Evidence for a role of Mycoplasma genitalium in pelvic inflammatory disease. Current Opinion in Infectious Diseases 21: 65–69.

Heymann DL and Aylward RB (2006) Mass vaccination: when and why. Current Topics in Microbiology and Immunology 304: 1–16.

Holst O, Ulmer AJ, Brade H, Flad HD and Rietschel ET (1996) Biochemistry and cell biology of bacterial endotoxins. FEMS Immunology and Medical Microbiology 16: 83–104.

Ishida N, Irikura D, Matsuda K et al. (2009) Molecular cloning and expression of a novel cholinephosphotransferase involved in glycoglycerophospholipid biosynthesis of Mycoplasma fermentans. Current Microbiology 58: 535–540.

Janeway CA Jr and Medzhitov R (2002) Innate immune recognition. Annual Review of Immunology 20: 197–216.

Kawahito Y, Ichinose S, Sano H et al. (2008) Mycoplasma fermentans glycolipid‐antigen as a pathogen of rheumatoid arthritis. Biochemical and Biophysical Research Communications 369: 561–566.

Keller MA and Stiehm ER (2000) Passive immunity in prevention and treatment of infectious diseases. Microbiology Reviews 13: 602–614.

Kitazawa K, Tagawa Y, Honda A and Yuki N (1998) Guillain–Barré syndrome associated with IgG anti‐GM1b antibody subsequent to Mycoplasma pneumoniae infection. Journal of the Neurological Sciences 156: 99–101.

Kusunoki S, Shiina M and Kanazawa I (2001) Anti‐Gal‐C antibodies in GBS subsequent to mycoplasma infection: evidence of molecular mimicry. Neurology 57: 736–738.

Lea‐Smith DJ, Martin KL, Pyke JS et al. (2008) Analysis of a new mannosyltransferase required for the synthesis of phosphatidylinositol mannosides and lipoarbinomannan reveals two lipomannan pools in corynebacterineae. Journal of Biological Chemistry 283: 6773–6782.

Levine SR, Brey RL, Sawaya KL et al. (1995) Recurrent stroke and thrombo‐occlusive events in the antiphospholipid syndrome. Annals of Neurology 38: 119–124.

Matsuda K (2004) Phosphocholine‐containing glycoglycerolipids of Mycoplasma fermentans as a pathogen of rheumatoid arthritis: possible role of Mycoplasma fermentans GGPLs in the pathogenesis of neuroendocrine‐immune abnormalities. Recent Research Development in Neurosciences 1: 15–23.

Matsuda K, Ishizuka I, Kasama T et al. (1997a) Structure of a novel phosphocholine‐containing aminoglycoglycerolipid of Mycoplasma fermentans. Biochimica et Biophysica Acta 1349: 1–12.

Matsuda K, Kasama T, Ishizuka I et al. (1994) Structure of a novel phosphocholine‐containing glycoglycerolipid from Mycoplasma fermentans. Journal of Biological Chemistry 269: 33123–33128.

Matsuda K, Li JL, Harasawa R and Yamamoto N (1997b) Phosphocholine‐containing glycoglycerolipids (GGPL‐I and GGPL‐III) are species‐specific major immunodeterminants of Mycoplasma fermentans. Biochemical and Biophysical Research Communications 233: 644–649.

Matsuda K, Li JL, Ichinose S et al. (2000) Monoclonal antibody against Mycoplasma fermentans‐specific aminoglycoglycerolipid. Microbiology and Immunology 44: 695–702.

Matsuda K, Taki T, Hamanaka S et al. (1993) Glycosphingolipid compositions of human T‐virus type I (HTLV‐I) and human emmunodeficiency virus (HIV)‐infected cell lives. Biochemica et Biophysica Acta 1168: 123–129.

Miyachi A, Miyazaki A, Shingu Y et al. (2009) Synthesis and absolute structures of Mycoplasma pneumoniae beta‐glyceroglycolipid antigens. Carbohydrate Research 344: 36–43.

Morath S, von Aulock S and Hartung T (2005) Structure/function relationships of lipoteichoic acids. Journal of Endotoxin Research 11: 348–356.

Nishida Y, Takamori Y, Matsuda K et al. (1999a) Synthesis of artificial glycoconjugate polymer carrying 6‐O‐phosphocholine‐α‐d‐glucopyranoside, biological active segment of main cell membrane glycolipids of Mycoplasma fermentans. Journal of Carbohydrate Chemistry 18: 65–72.

Nishida Y, Takamori Y, Ohrui H et al. (1999b) Synthesis and absolute configulation of a novel aminoglycoglycerolipid, species‐specific immunodeterminant of Mycoplasma fermentans. Tetrahedron Letters 40: 2371–2374.

Nussinovitch U (2010) The association between mycoplasma infections and atherosclerosis: myth or clinical reality? Israel Medical Association Journal 12: 439–440.

Porcelli SA and Modlin RL (1999) The CD1 system: antigen‐presenting molecules for T cell recognition of lipids and glycolipids. Annual Review of Immunology 17: 297–329.

Raetz CRH (1990) Biochemistry of endotoxins. Annual Review of Biochemistry 59: 129–170.

Rees JH, Soudain SE, Gregson NA and Hughes RA (1995) Campylobacter jejuni infection and Guillain–Barré syndrome. New England Journal of Medicine 333: 1374–1379.

Rivera A, Yáñez A, León‐Tello G et al. (2002) Experimental arthritis induced by a clinical Mycoplasma fermentans isolate. BMC Musculoskeletal Disorders 3: 15–21.

Salio M, Silk JD and Cerundolo V (2010) Recent advances in processing and presentation of CD1 bound lipid antigens. Current Opinion in Immunology 22: 81–88.

Silk JD, Salio M, Brown J, Jones EY and Cerundolo V (2008) Structural and functional aspects of lipid binding by CD1 molecules. Annual Reviews in Cell and Developmental Biology 24: 369–395.

Susuki K, Odaka M, Mori M, Hirata K and Yuki N (2004) Acute motor axonal neuropathy after Mycoplasma infection: evidence of molecular mimicry. Neurology 62: 949–956.

Svennerholm L (1963) Chromatographic separation of human brain gangliosides. Journal of Neurochemistry 10: 613–623.

Wack A and Rappuoli R (2005) Vaccinology at the beginning of the 21st century. Current Opinion in Immunology 17: 411–418.

Waites KB and Talkington DF (2004) Mycoplasma pneumoniae and its role as a human pathogen. Clinical Microbiology Reviews 17: 697–728.

Further Reading

Alberts B, Johnson A, Lewis J et al. (eds) (2008) Molecular Biology of the Cell, 5th edn. New York: Garland Science.

Barile MF and Razin S (eds) (1979) Cell biology. The Mycoplasmas, vol. 1. London: Academic Press.

Cazes J (ed.) (2005) Encyclopedia of Chromatography, 2nd edn. London: Taylor & Francis Group.

Cherry J, Kaplan S, Demmler‐Harrison G and Steinbach W (eds) (2009) Feigin and Cherry's Textbook of Pediatric Infectious Diseases, 6th edn. Philadelphia: Saunders.

Delves P, Martin S, Burton D and Roitt I (eds) (2006) Roitt's Essential Immunology, 11th edn. Hoboken, NJ: Wiley‐Blackwell.

Fauci AS, Braunwald E, Kasper DL et al. (eds) (2008) Harrison's Principles of Internal Medicine, 17th edn. London: The McGraw‐Hill Companies.

Firestein GS, Budd RC, Harris ED Jr et al. (eds) (2008) Kelley's Textbook of Rheumatology, 8th edn. Philadelphia: Saunders.

Murphy KM, Travers P and Walport M (eds) (2007) Janeway's Immunobiology, 7th edn. New York: Garland Science.

Rich R, Fleisher T, Shearer W, Kotzia B and Schroeder H Jr (eds) (2008) Clinical Immunology: Principles and Practice, 3rd edn. London: Mosby International Limited.

Roitt I and Delves P (eds) (1998) Encyclopedia of Immunology, 2nd edn. Oxford: Elsevier limited.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Matsuda, Kazuhiro(Dec 2011) Antigens: Lipids. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000501.pub3]