The canonical functions of antibodies are based on joining the process of antigen recognition with initiation of innate immune reactions. With the introduction of modern research approaches, and the use of sophisticated model systems, the recent years have witnessed the discovery of numbers of non-canonical functions of antibodies. These functions encompass either untypical strategies for neutralization of pathogens or exertion of activities by antibodies that are typically characteristic for other proteins (cytokines, chaperons or enzymes). Here we provide an overview of non-canonical functions of antibodies and discuss their mechanisms and implications for immune regulation and immune defence. A better comprehension of these functions will enrich our knowledge about the adaptive immune response and shall inspire the development of novel therapeutics.
HighlightsAntibodies are major player in adaptive immunity. They participate in immune defence and have potent immune-modulatory potential.Antibody molecules have two functional centresthey bridge the specific antigen recognition through antigen-binding site with interaction and activation of innate immune receptors, via their constant regions. These integrated interactions are essential for the classical antibody functions.Antibodies can utilize alternative or non-canonical strategies for broadening of their functional competency. Thus antibodies perform untypical activities by acquiring activities typical for cytokines, chaperones, transporters, enzymes etc.
HighlightsThe structure determines the functions of antibodies Antibodies are protagonists of the adaptive immunity with key roles in immune defence and in immune regulation. They are produced by B lymphocytes, which undergo complex lifecycle that culminates in differentiation into antibody-secreting plasma cells. The characteristic molecular organization of immunoglobulin molecules, namely the presence of two functionally distinct poles: an antigen-binding site and a constant region (BOX 1), determines most of the biological functions of antibodies.Thus, the prototypical property of antibodies is their potential to link antigen recognition, mediated by the variable regions, with engagement of different types of innate immune proteins (Fc receptors (FcR), C1q, TRIM21), through the constant region. These interactions trigger diverse sets of biological reactions (Figure 1) (Lu et al., 2018).Although relatively invariant as compared to the variable region, the constant (or Fc) regions of different antibody molecules display certain heterogeneity. Thus, as based on sequence differences in the constant portion of the heavy chain, five immunoglobulin classes are identified in humans -IgG, IgA, IgM, IgD and IgE (Schroeder and Cavacini, 2010, Vidarsson et al., 2014). Moreover, IgG and IgA classes are subdivided into subclasses -IgG1, IgG2, IgG3 and IgG4 as well as IgA1 and IgA2, respectively. Each immunoglobulin class or subclass has preferential binding to different types of receptors for the constant region (FcR)...