Antigens and Immunogens

Lect-5 (BCH-606)
 Antigens/Immunogens

• Immunogen: a stimulus (any agent) that produces a

humoral or cell-mediated immune response
• Antigen: any substance that binds specifically to an
antibody or a T-cell receptor
All immunogens are antigens but not all antigens are
immunogens
• Hapten: a low molecular weight molecule (can bind to
Abs and TCRs) that can be made immunogenic by
conjugation to a suitable carrier (high molecular weight)
 Haptens are not immunogenic…Why?
• Because they cannot activate helper T cells.
• The inability of haptens to activate is due to
being unable to bind with MHC proteins, only
polypeptides can bind.
• As they are univalent, can’t activate B cells.
• Can stimulate primary or secondary response
when bound to a carrier protein. (Fig 57.5)
• Conjugate vaccine based on hapten-carrier
protein concept
 Epitope/Paratope
• Epitope: the portion of an antigen that is
recognized and bound by an Ab or TCR/MHC
complex.
• Paratope…

• Paratope: “The site in the variable (V) domain

of an antibody or T-cell receptor that binds to
an epitope on an antigen
 Factors Influencing Immunogenicity

• Contribution of immunogen
1. Foreignness
2. Molecular size
3. Chemical complexity & heterogeneity
4. Degradability
 1-Foreignness
• The first requirement for a compound to be
immunogenic is foreignness. A processed
antigen in an MHC is seen by a TCR.

• Autoimmunity: When an individual mounts an

immune response against his or her own
tissue
 2-High Molecular weight

• Compounds with a molecular weight < 1000Da

not immunogenic
• With a molecular weight b/w 1000 & 6000Da
may or may not immunogenic
• With a molecular weight > 6000Da generally
immunogenic
 3-Chemical Complexity

• For a compound to be immunogenic certain degree of

physiochemical complexity is required (e.g., amino acid
homopolymers are less immunogenic than heteropolymers
containing two or three different amino acids).

• For example homopolymers of lysine(30,000Da),

polyglutamic acid (50,000Da) are seldom good
immunogens.
• However copolymers (by attachment of various moieties of
polyglutamic, alanine and lysine (poly-GAT) tend to be
highly immunogenic.
 4-Degradability

• Ag processing by Ag Presenting Cells (APC)

(enzymatic degradation of antigen before they
can express antigenic epitopes and stimulate
helper T cells. The APCs have MHC proteins to
which “processed” fragments of the protein
can bind non-covalently. This complex is then
presented to TCRs which are activated.
 B- Contribution of Biological System
• Genetics
• Age
 C- Dosage, Route, and Timing of Antigen Administration

• These factors also affect immunogenicity. In

addition, the genetic constitution of the host
(HLA genes) determines whether a molecule is
immunogenic.
• Different strains of the same species of animal
may respond differently to the same antigen.
 Antigenicity

• Antigenicity refers to the ability of a compound to

bind with antibodies or with cells of the immune
system
• The binding between antigen and immune
components involves several weak forces operating
over short distances (van der waals forces,
electrostatic interactions, hydrophobic interactions
and hydrogen bonds); it does not involve covalent
bonds
 Major Classes of Immunogens

• Proteins: Best immunogens

• Carbohydrates: Usually but not always good

immunogens

• Nucleic Acids: Poor immunogens by themselves

unless coupled to carriers

• Lipids: Non immunogens unless coupled to carriers

 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
 Sequential (or linear) determinants

• Epitopes formed by several adjacent amino

acid residues are called linear determinants.
• They exist on the surface of antigen molecules
or inside of antigen molecules.
• They are mainly recognized by T cells, but
some can also be recognized by B cells.
 Conformational determinants
• Conformational determinants are formed by
amino acid residues that are not in a sequence
but become spatially juxtaposed in the folded
protein.
• They normally exist on the surface of antigen
molecules.
• They are recognized by B cells or antibody
 Antigenic Determinants Recognized by B cells and Ab

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

• Size
- 4-8 residues
 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 to MHC
 Cross Reactivity

• An immunologic reaction in which the immune

components, either cells or antibodies, react with
two molecules that share epitopes, but are otherwise
dissimilar is called a cross-reaction.
• Modification of a molecule; toxins and toxoids

• Sharing epitopes between unrelated macromolecules

• Structural resemblance (molecular mimicry)

 Adjuvants

• Substances which when mixed with an immunogen

enhance the immune response against the immunogen

• They differ from carriers as they do not enhance

immunity to haptens

• Release immunogens slowly but continuously

• Types: Freund’s incomplete or complete adjuvants,
BCG, Corynebacterium parvum, Bordetella pertussis,
LPS, and Alum precipitate (most widely used )