A. George-chandy et al., Cholera toxin B subunit as a carrier molecule promotes antigen presentation and increases CD40 and CD86 expression on antigen-presenting cells, INFEC IMMUN, 69(9), 2001, pp. 5716-5725
Cholera toxin B subunit (CTB) is an efficient mucosal carrier molecule for
the generation of mucosal antibody responses and/or induction of systemic T
-cell tolerance to linked antigens. CTB binds with high affinity to GM1 gan
glioside cell surface receptors. In this study, we evaluated how conjugatio
n of a peptide or protein antigen to CTB by chemical coupling or genetic fu
sion influences the T-cell-activating capacity of different antigen-present
ing cell (APC) subsets. Using an in vitro system in which antigen-pulsed AP
Cs were incubated with antigen-specific, T-cell receptor-transgenic T cells
, we found that the dose of antigen required for T-cell activation could be
decreased >10,000-fold using CTB-conjugated compared to free antigen. In c
ontrast, no beneficial effects were observed when CTB was simply admixed wi
th antigen. CTB conjugation enhanced the antigen-presenting capacity not on
ly of dendritic cells and B cells but also of macrophages, which expressed
low levels of cell surface major histocompatibility complex (MHC) class II
and were normally poor activators of naive T cells. Enhanced antigen-presen
ting activity by CTB-linked antigen resulted in both increased T-cell proli
feration and increased interleukin-12 and gamma interferon secretion and wa
s associated with up-regulation of CD40 and CD86 on the APC surface. These
results imply that conjugation to CTB dramatically lowers the threshold con
centration of antigen required for immune cell activation and also permits
low-MHC II-expressing APCs to prime for a specific immune response.