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Chapter 4 – AntigenRecognition in theAdaptive Immune

System

Dr. Hafez Sumairi

Learning outcomes

1.How do the antigen receptors of lymphocytesrecognize extremely diverse antigens and transmitactivating signals to the cells?

2.What are the differences in the recognitionproperties of antigen receptors on B cells and Tcells?

3.How is the vast diversity of receptor structures inthe lymphocyte repertoire generated?

Antigen receptors of lymphocytes

• Antigen receptor molecules consist of• Variable (V) regions (domains) involved in antigen recognition—and

therefore varying between clones of lymphocytes• Hypervariable regions, or complementarity determining regions (CDRs)

• Constant (C) regions required for structural integrity and effectorfunctions—and thus relatively conserved among all clones.

• Antigen receptor chains are associated with invariant membraneproteins whose function is to deliver intracellular signals that aretriggered by antigen recognition

Antigen receptors of lymphocytes

Antibodies• An antibody molecule is composed of four

polypeptide chains are assembled to form a Y-shaped,

• Two identical heavy (H) chains called µ, δ, γ, ε, and α• Two identical light (L) chains either κ or λ• Each chain containing a variable region and a constant

region

• The antigen-binding site of an antibody iscomposed of

• V regions of both the heavy chain (called VH) and thelight chain (called VL) contains three hypervariableregions, or CDRs.

• Two identical Fab (fragment, antigen binding)

• One Fc (fragment, crystalline)• Biologic activity and effector functions of the antibodies

• Between the Fab and Fc regions called the hingeregion

Antibodies• Different classes, or isotypes, and are named

according to their heavy chains (IgM, IgD, IgG, IgE,and IgA)

• Change in Ig isotype production is called heavy-chainclass (or isotype) switching

• Antibodies are capable of binding a wide variety ofantigens

• Antibodies bind to antigens by reversible,noncovalent interactions,

• Hydrogen bonds,• Hydrophobic interactions,• Charge based interactions

• The parts of antigens that are recognized by antibodiesare called epitopes, or determinants.

• Linear epitopes• Conformational epitopes

• Affinity is the strength of an antibody binds to oneepitope of an antigen

• Avidity is the total strength of binding

• Cross-reaction is the binding to structurally similarepitopes

• One clone of B cells makes an antibody of only onespecificity (monoclonal antibodies)

Monoclonalantibodies• Fused cells derived from

the B cells and themyeloma, which are calledhybridomas

• Use as therapeutic anddiagnostic reagents

T cell receptors for antigens

• Both the α chain and the βchain of the TCR participate inspecific recognition of MHCmolecules and bound peptides

Antigen recognitionAntigen recognition issimilar for B and Tlymphocyte receptors

TCRs are not produced in asecreted form and do notundergo class switching oraffinity maturation duringthe life of a T cell.

Development ofimmunerepertoires

Early lymphocyte development

• Immature lymphocytes undergoproliferation at several stagesduring their maturation

• Stimulated mainly by thegrowth factor IL7

• Antigen receptors are encoded byseveral gene segments that areseparate from one another in thegermline and that recombineduring lymphocyte maturation.

• Lymphocytes are selected atmultiple steps during theirmaturation to preserve the usefulspecificities

Production of diverseantigen receptors• The formation of functional

genes that encode B and Tlymphocyte antigen receptors isinitiated by somaticrecombination of gene segmentsthat code for the variable regionsof the receptors, and diversity isgenerated during this process.

• All antigen receptor gene locicontain V, J, and C genes, butonly the Ig heavy chain and TCRβ chain loci also contain D genesegments.

Production of diverseantigen receptorsThe somatic recombinationof V and J, or of V, D, and J,gene segments is mediated bya lymphoid specific enzyme,VDJ recombinase, andadditional enzymes, most ofwhich are not lymphocytespecific and are involved inrepair of double strandedDNA breaks.

Maturation and selection of B lymphocytes

• The maturation of Blymphocytes occursmainly in the bonemarrow

• The IgM expressing Blymphocyte is theimmature B cell.

• The IgM+IgD+cell isthe mature B cell

Maturation andselection of Tlymphocytes• The most immature progenitors

are called pro-T cells ordouble-negative T cells (ordouble negative thymocytes)because they do not expressCD4 or CD8.

• The complete αβ TCR and boththe CD4 and CD8 coreceptors;these cells are called double-positive T cells (or double-positive thymocytes).

Thank you