Febrile temperatures increase in vitro antibody affinity for malaria and dengue antigens

Abstract

Fever is a regulated elevation in the body setpoint temperature and may arise as a result of infectious and noninfectious causes. While beneficial in modulating immune responses to infection, the potential of febrile temperatures in regulating antigen binding affinity to antibodies has not been explored. We have investigated this process under in vitro conditions using selected malaria or dengue antigens and specific monoclonal antibodies, and observed a marked increase in the affinity of these antibody-antigen complexes at 40˚C, compared to physiological (37˚C) or pathophysiological temperatures (42˚C). Induced thermal equilibration of the protein partners at these temperatures, prior to measurements, further increased their binding affinity. These results may indicate an unexpected beneficial and adaptive role for fever in vivo, and highlight the positive role of thermal priming in enhancing protein-protein affinity for samples of scarce availability.

Molecular memory of periodic thermal stimulation in an immune complex

“…Furthermore, we demonstrate that following application of temperature waveforms, the memory of these periodic external events is manifested in the absence of the original stimulus and may form the basis of a molecular predictive capacity. [4]. We measured in vitro by calorimetric techniques the thermodynamic parameters of their binding upon cycles of thermal entrainment at 25 and 37 , prior to or after complex formation.…”

“…Isothermal titration calorimetry (ITC) was used to assess the binding affinity changes in proteins during their complex formation (Figure 1), in the absence (red-colored thermogram) or presence (blue-colored signal) of the periodic thermal entrainment of 10 minutes cycles at each indicated temperature prior to titrations. In contrast to the expected endothermic reaction described by a sigmoid curve [4], the thermograms obtained for the MSP1 19 titrated into K 2 [5]. Importantly, the phase of the oscillation in the binding affinity curve was advanced compared to a fitted harmonic wave [SI], an observation that may explain a similar phase shift measured in vitro with other systems, upon temperature increase but on a lengthier circadian basis [6].…”