Carbohydrates and Lipids

Carbohydrate polymers have been known to be antigenic since the beginnings of the study of immunology. They are commonly encountered in pathogenic organisms, such as pneumococci, and it is to be expected that there has been substantial evolutionary pressure to produce effective responses against them (reviewed by Berzofsky and Berkower, 1993). As a general rule, low molecular weight carbohydrates are not immunogenic, but may become so after coupling to an immunogenic carrier. The carbohydrate moieties of glycoproteins and glycolipids are also immunogenic. Other important carbohydrate antigens include the ABO blood group substances, which are glycolipid in nature (Yamamoto et al., 1990). For background information on carbohydrate antigens, the reader is referred to the reviews of Wiegandt (1985), Sharon and Lis (1989,1993), Karlsson (1991) and Drickamer and Carver (1992)

The manner in which carbohydrate antigens stimulate the immune system is somewhat different to that of proteins. A classical example of a carbohydrate antigen is bacterial lipopolysaccharide (LPS). LPS has intrinsic mitogenicity for B cells, owing to its lipid A moiety. It also has potent adjuvant properties, and is capable of inducing endotoxic shock, which may be fatal. LPS binds to a serum protein known as LPS-binding protein (LBP; Schumann et al., 1990), which then binds to the CD 14 molecule on the surface of monocytes and neutrophils (Wright et al., 1990; Ferrero et al., 1993), activating them and causing the release of cytokines including tumour necrosis factor a (TNF-a), a primary mediator of endotoxic shock (Beutler and Cerami, 1988; Bone, 1991). LPS also has potent immunological adjuvant activity.

Although many carbohydrate antigens are capable of eliciting very high titre antibodies, and these may be of the IgG class, the question of whether T cells can recognize carbohydrates has been controversial. Paradoxically, one of the reasons for this controversy has been the progress in understanding the role of the histocompatibility antigens in presenting antigen to T cells. As the mechanism of peptide binding to MHC proteins became clear, it became less clear how carbohydrates could bind. However, there is now a considerable and growing body of evidence that some T cells can recognize carbohydrate or glycolipid antigens (Litvin et al., 1981; Moll et al., 1989; Michaelsson et al., 1994; Haurum et al., 1994; Tanaka et al., 1994; Beckman et al., 1994; Bendelac, 1995; Sieling et al., 1995). In many such cases, recognition by T cells is not MHC restricted, or is restricted by the so-called non-classical (class lb) MHC molecules. In some cases the relevant T cells have been shown to bear yb receptors for antigen (Strominger, 1989; Hedrick, 1992; Parham; 1994; Klein and O'hUigin, 1994; Beckman et al., 1994).

In addition to their intrinsic interest and importance, carbohydrate antigens can be the cause of experimental artefacts. For example, the carbohydrate moiety on one glycoprotein may be identical in structure to that on an unrelated glycoprotein, and be the source of serological cross-reaction between them. It has recently been shown that antibodies to galactosyl determinants may bind to agarose, a commonly used support matrix for affinity chromatography (Osborn et al., 1994). If the presence of such antibodies is not recognized, they could be the source of misleading observations.

The fact that lipids are hydrophobic and tend to form micelles and membranes may make them less accessible to the immune system than more hydro-philic molecules such as carbohydrates and proteins. The degree to which the immune system can respond to lipids has been somewhat controversial, although as early as the 1940s, there was considerable evidence that sterols can be immunogenic when attached to large carrier proteins (Landsteiner, 1962; Aniagolu et al., 1995 and references therein). Similarly, antibodies to steroid hormones may be raised by immunization with these molecules bound to immunogenic protein carriers, and these antibodies have been widely used for radioimmunoassay.

There seems to be no reason in principle why the immune system should not see the more hydrophilic portions of lipid-containing molecules, such as hydroxyl, phosphate or carbohydrate groups (Bendelac, 1995; Sieling et al., 1995). The extent to which the more hydrophobic portions of such amphi-pathic molecules are seen by the immune system is currently rather unclear. Antibodies to phospholipids such as cardiolipin are commonly said to be found in patients with systemic lupus erythematosus, but their specificity may be directed to protein:lipid complexes rather than the lipids in isolation (Roubey, 1994; Harris et al., 1995 and references therein).

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment