title: Thermodynamic stability contributes to immunoglobulin specificity.
abstract: Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies.
authors.affiliation: INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France; Université Paris Descartes, UMRS 1138, Paris, France; Université Pierre et Marie Curie (UPMC)-Paris 6, URMS 1138, Paris, France. Electronic address: jordan.dimitrov@crc.jussieu.fr.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
authors.affiliation: INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France; Université Paris Descartes, UMRS 1138, Paris, France; Université Pierre et Marie Curie (UPMC)-Paris 6, URMS 1138, Paris, France.
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France; Université Paris Descartes, UMRS 1138, Paris, France; Université Pierre et Marie Curie (UPMC)-Paris 6, URMS 1138, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology*; D055550:Protein Stability; D013816:Thermodynamics
chemical_list: D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins
keywords: conformational dynamism; immunoglobulins; interaction promiscuity; thermodynamic stability