The influence of natural antibody specificity on antigen immunogenicity

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Abstract
The natural antibody repertoire in humans, apes and Old World primates is distinct from the repertoire of all other placental mammals, and encodes antibodies specific for the carbohydrate epitope Galα1–3Galβ1–4GlcNAc‐R (αGal). Here, we examined whether conjugating antigens to the αGal epitope can augment their immunogenicity in α(1,3)galactosyltransferase knockout mice (GT0 mice) which, like humans, produce αGal‐specific antibodies. Immunization of GT0 mice with BSA conjugated to αGal (αGal‐BSA) led to significant production of anti‐BSA IgG antibodies without the need for adjuvant. This response was dependent on the presence of αGal‐reactive antibodies. Immunization of wild‐type mice with αGal‐BSA failed to induce an anti‐BSA response. The presence of αGal‐reactive antibodies also led to an increase in the T cell response to BSA following immunization with αGal‐BSA when compared with mice that received BSA alone, resulting in an increased frequency of IFN‐γ− and IL‐4‐producing BSA‐specific T cells. In addition, the ability to produce αGal‐reactive antibodies enhanced the cytotoxic T lymphocyte anti‐viral antigen response following vaccination with murine leukemia virus transformed cell lines that express αGal on their cell surface. Natural antibodies that bind αGal therefore play a key role in increasing the efficiency of priming to antigens decorated with αGal epitopes.