Antigens

Jennifer Nyland, PhD Office: Bldg#1, Room B10 Phone: 733-1586 Email: jnyland@uscmed.sc.edu

Teaching objectives
To compare and contrast immunogen, antigen & hapten To describe the factors influencing immunogenicity To define the chemical nature of immunogens To compare the structures of T-independent and Tdependent antigens To introduce the concept of hapten-carrier conjugates and their structure To characterize antigenic determinants To define superantigens

Overview of the immune system

Immune system

Innate (nonspecific) 1st line of defense

Adaptive (specific) 2nd line of defense

Cellular components

Humoral components

Cellular components

Humoral components

Vocabulary
Immunogen Antigen (Ag) Hapten Epitope or antigenic determinant Antibody (Ab)

Factors influencing immunogenicity

Factors

Contribution of immunogen

Contribution of biological system

Method of administration

Immunogenicity: contribution of immunogen

Foreignness Size Chemical composition
Primary structure --- sequence determinants Secondary structure Conformational Tertiary structure determinants Quarternary structure

Immunogenicity: contribution of immunogen

Foreigness Size Chemical composition Physical form
Particular > Soluble Denature > Native

Immunogenicity: contribution of immunogen

Foreigness Size Chemical composition Physical form Degradability
Ag processing by Ag-presenting cells (APC)

Immunogenicity: contribution of biological system

Genetics
Species Individual
Responders vs Non-responders

Age

Immunogenicity: method of administration

Dose Route
Subcutaneous > Intravenous > Intragastric

Adjuvant
Substances that enhance immune response to Ag

Chemical nature of immunogen

Proteins Polysaccharides Nucleic acids Lipids
Some glycolipids and phospholipids can be immunogenic for T cells and illicit a cell-mediated immune response

Antigens: T-independent
Activate B cells without MHC class II T help Polysaccharides Properties
Polymeric structure Polyclonal B cell activation, but poor memory Resistance to degradation

Examples
Pneumococcal polysaccharide, LPS Flagella

Antigens: T-dependent
Require T help to activate B cells Proteins Structure Examples
Microbial proteins Non-self or altered-self proteins

Hapten-carrier conjugates
Definition
Ag only if bound to carrier protein

Structure
Native determinants Haptenic determinants

Antigenic determinants recognized by B cells and Ab

Composition
Proteins, polysaccharides, nucleic acids, haptens Sequence (linear) determinants Conformational determinants

Size
4-8 residues

Antigenic determinants recongized by B cells and Ab

Composition Size Number
Limited (immunodominant epitopes) Located on the external surface of the Ag (exposed)

Antigenic determinants recognized by T cells

Composition
Proteins (some lipids) Sequence determinants
Processed MHC presentation (lipid presentation by MHC-like CD1)

Size
8-15 residues

Number
Limited to those that can bind MHC

Superantigens
Definition
T cell
TCR Ag MHC APC MHC APC

T cell
TCR

Polyclonal T cell response

SuperAg

Examples
Staphlycoccal enterotoxins Toxic shock toxin

Summary of immune response

Adaptive immune response
Discrete determinants Reacts with specific pathogen

Innate immune response

Broad molecular patterns Reacts with a variety of pathogens