Abstract
It was recognized early last century that small molecules, known as haptens, can be made immunogenic after conjugation to carrier proteins (1). This principle has since been applied successfully to improve the immunogenicity of (poly)saccharides (2,3). We now know that the carrier proteins ensure the involvement of T-helper lymphocytes in the activation of the hapten- or polysaccharide-specific antibody-producing B lymphocytes (Fig. 1). In contrast to small molecules or haptens, polysaccharides (or other macromolecules with a repeating structure) are able to induce an immune response, most likely by directly activating B-lymphocytes. Antigens that are able to induce an immune response without the involvement of T-helper lymphocytes are referred to as TI (thymus-independent) antigens (4) (Table 1). TI-2 antigens, such as plain polysaccharides, are not able to activate relatively immature B-cells. This is in contrast to TI-l antigens, which can activate immature B-cells because of their mitogenic activity. Lipopolysaccharides (LPS) are examples of TI-l antigens. Conventional T-cells recognize peptide sequences in association with the major histocompatibility complex (MHC). Recently, unconventional T-cells were found to recognize (glyco) lipids in a CD1-restricted way, γδT-cells were shown to respond to non-proteinaceous microbial ligands (that may include carbohydrates) in a virtually MHC-unrestricted way (5). The findings of T-cell regulation of the immune response against polysaccharides (6–8) without biochemical demonstration of the specificity of the molecular interactions can best be explained by assuming a role for anti-idiotypic antibodies and T-cells specific for the idiotopes (carbohydrate mimotopes) or via the newly discovered unconventional T-cells.
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Peeters, C.C.A.M. et al. (2003). Preparation of Polysaccharide-Conjugate Vaccines. In: Robinson, A., Hudson, M.J., Cranage, M.P. (eds) Vaccine Protocols. Methods in Molecular Medicine™, vol 87. Humana Press. https://doi.org/10.1385/1-59259-399-2:153
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DOI: https://doi.org/10.1385/1-59259-399-2:153
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