General antibody structure
Enzyme digestion fragments
Protein structure of immunoglobulins
• Early amino acid sequence experiments were unsuccessful—too much variation
• Multiple myeloma serum is 95% same antibody• Bence-jones protein found in urine of myeloma
patients is excess light chain• 110 amino acids highly variable, rest are quite
constant• 5 different isotypes identified: based on type of
heavy chain: G,D,E,M,A• Human light chains: 60% kappa (K) chains, 40%
lambda (L) chains
Detailed structure of antibody
Ribbon model of variable region
• Variable region contains highly variable connecting regions called complementarity-determining regions or CDRs
• These regions are also shown to be the antigen binding sites
Amino acid diversity of variable domains – complementarity- determining regions (CDRs)
Antigen – antibody interaction
Hiv protease and Fab fragmentConformational change in Fab
domain
General structures of different antibody classes
• Isotype – different species
• Allotype – same species, different alleles
• Idiotype – same species, different VH and VL domains
Isotypic determinants – different species variation within the
constant region
Allotypic determinants – different constant regions within the same
species – different alleles
Idiotypic determinants – variations in the variable region within the
same antibody type
Fc receptors – bind Fc portion of antibody molecules
Immunoglobulin superfamily of cell receptors – evolved from common
ancestor gene
More members of the Ig superfamily
Many uses for monoclonal antibodies
Antibodies can deliver drugs to specific targets