MLRS 242 Immunology Pat Reed Antibodies

Serum proteins

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

Ribbon model of antibody

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

Model of antibody

Amino acid diversity of variable domains – complementarity determining regions (CDRs)

Antigen – antibody interaction

Space filling model

Hiv protease and Fab fragment Conformational change in Fab domain

General structures of different antibody classes

Subclasses of IgG

Secretory IgA

Receptor bound IgE

• Isotype – different species • Allotype – same species, different alleles • Idiotype – same species, different V H and V L 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

B Cell Receptor - BCR

Fc receptors – bind Fc portion of antibody molecules

Immunoglobulin superfamily of cell receptors – evolved from common ancestor gene

More members of the Ig superfamily

Monoclonal antibodies

Many uses for monoclonal antibodies

Antibodies can deliver drugs to specific targets