title: Primitive vertebrate immunity: what is the evolutionary derivative of molecules that define the adaptive immune system?
abstract: The adaptive immune system is capable of responding to an infinite number of antigens with the antigen-specific receptors immunoglobulin (Ig) and the T cell receptor (TCR). Ig binds soluble antigens while TCR recognizes antigen bound in clefts of polymorphic self-encoded major histocompatibility complex (MHC) class I and class II molecules. All of these molecules are wholly or partially composed of Ig superfamily domains. TCR and Ig use V-set Ig superfamily domains, always in heterodimeric forms, in antigen recognition. Although the ways in which TCR and Ig bind antigen are fundamentally different, the structure of the heterodimeric V domains is probably identical. The antigen-binding cleft of MHC proteins has a structure unlike Ig superfamily domains, although several investigators have proposed that this cleft is evolutionarily derived from Ig domains. We believe the MHC cleft is a primitive structure, perhaps related to the peptide-binding domains of intracellular chaperone proteins. A model is proposed whereby chaperone proteins were the primordial MHC molecules, presenting peptides derived from invariant proteins residing inside cells for recognition by lymphocytes with minimally diverse receptors. Such a system may be reflected today by the epithelial immune system, apparently governed by monomorphic MHC molecules and lymphocytes with unconventional antigen-specific receptors.
authors.affiliation: Department of Microbiology and Immunology, University of Miami, FL 33136, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Flajnik
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology*; D000818:Animals; D005075:Biological Evolution; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014714:Vertebrates / Q000276:immunology*
chemical_list: D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell