Further studies are needed to investigate whether ACPA-IgG autoantibodies of high avidity are indeed produced by bone marrow derived plasma cells or whether other mechanisms are responsible for the differences in avidity of ACPA autoantibodies, for instance consumption of high avidity ACPA-IgG autoantibodies at sites of synovial inflammation.
Induction of high avidity, BoNT/A-neutralizing antibodies required the use of adjuvants (CT or C48/80) and future studies will work to optimize vaccine formulations and adjuvants for their ability to induce high-avidity antibodies.
In order to determine if CD25+ Tregs may be preventing or regulating the development of high avidity memory immunity, anti-CD25 monoclonal antibodies were used to deplete Tregs prior to immunization.
The increased potency of high avidity CD8+ T cells for the clearance of viral infections has been well documented.
Importantly, DNA vaccination mediated the generation of high avidity neutralizing antibodies that mediated protection against lethal toxin challenge.
The phenomenon of apparent deletion of high avidity CTLs has been observed in other clinical scenarios.
Consistent with a previous report of an avidity threshold for killing by specific CTL [11], [34], our data suggest that cross-reactivity is more likely to suppress the growth of high avidity variants.
For instance, we have shown that CML shapes host immunity by preferential elimination of high avidity PR1-CTL, which are more cytolytic against CML than low avidity PR1-CTL, and the data in Figure 6 support these previous observations [24].
AI <50%% corresponds to reactivity with antibodies of low avidity, while AI > 75%% corresponds to reactivity with antibodies of high avidity.
However, IgG antibodies of high avidity specific to 60 kDa fraction were not detected (Fig. 8c).
