Immunogenic properties of immunoglobulin superfamily members within complex biological networks

Abstract

Antibodies, T cell receptors and major histocompatibility complex molecules are members of the immunoglobulin superfamily and have pivotal roles in the immune system. The fine interrelation between them regulates several immune functions. Here, we describe lesser-known functions ascribed to these molecules in generating and maintaining immune response. Particularly, we outline the contribution of antibody- and T cell receptor-derived complementarity-determining region neoantigens, antigenized antibodies, as well as major histocompatibility complex class I molecules-derived epitopes to the induction of protective/therapeutic immune responses against pathogens and cancer. We discuss findings of our own and other studies describing protective mechanisms, based on immunogenic properties of immunoglobulin superfamily members, and evaluate the perspectives of application of this class of immunogens in molecular vaccines design.

Keywords: Anti-idiotype; Complementarity-determining region; Immune network; Immunoglobulin; MHC; TCR.

Fig. 1

Basic interactions between Ig superfamily members within immunological network. (A) According to Jerne’s network theory, an antibody (Ab2) can bind to the variable region of antigen (Ag)-specific Ab (Ab1) and trigger a successive cascade of anti-anti-antibody production (Ab3). The anti-idiotypic Ab2 carries the internal image/mimotopes of the original Ag in CDRs and is capable to generate anti-anti-idiotypic B and T cell responses reinforcing the immune response to the original Ag. This class of immunogens (Ab2) was used as a vaccine against cancer and several pathogens. Similarly, the TCR beta chain (idiotypic TCR) generates TCR-specific Ab and anti-idiotypic Ag-specific T cell responses. (B) In transplant rejection, within graft-versus-host (GVH) interactions, apparently both auto- and allo-immunity are involved. The B cells produce MHC and non-MHC Abs, as well as Abs against mismatched minor Histocompatibility Antigens (mHC). The T cells can damage the graft by directly recognizing donor’s MHC or by eliminating target cells through p-MHC/TCR interaction, where peptides are derived from MHC molecules (undirect recognition). By a similar manner, the T cells may eliminate tumor cells through recognition of self MHC-derived peptides. (C) The antigenized Abs are immunoglobulins where T cell epitopes are inserted within CDRs, which convert them in effective vaccine immunogens targeting pathogens and tumor cells.