Immune Responses to Bacterial Polysaccharides: Terminal Epitopes Are More Immunogenic Than Internal Structures

Two types of dextran-protein conjugates can be produced depending on the size of dextran and the method chosen for coupling. Dextran of 4 × 104 molecular weight, randomly coupled to keyhole limpet hemocyanin evoked "incomplete" T cell-dependent (TD) immune responses. This atypical response only affected the dextran epitope since the response to the protein carrier was as expected for TD secondary immune responses. A second type of TD conjugates can be derived by coupling dextran (Dx) of 103 Da to the protein chicken serum albumin (CSA) via the reducing end (CSA-Dx-1). Immunization with CSA-Dx-1 induced the classical pattern of TD immune responses. Interestingly, immunization with CSA-Dx-1 favored the production of antibodies directed against terminal structures of the dextran molecule. These results were also confirmed at the hybridoma cell level. In contrast to other protein-dextran conjugates, CSA-Dx-1 was able to induce anti-dextran antibodies in CBA/N mice and in neonatal animals. We have interpreted these results to mean that conjugates exposing carbohydrate terminal nonreducing end structures could be more "physiological" and able to be recognized by helper T cells. This opens a new possibility for the production of vaccines against bacterial polysaccharides.