MLRS 242Immunology

Pat ReedAntibodies

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 fragmentConformational 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 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

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