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Lecture 15 Antigen Recognition

Lecture 15 Antigen Recognition. Overview. In order to initiate an immune response antigen must be recognized . Antigen recognition depends on detection of antigen by special receptors . Antigen recognition depends on cellular cooperation .

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Lecture 15 Antigen Recognition

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  1. Lecture 15Antigen Recognition

  2. Overview • In order to initiate an immune response antigen must be recognized. • Antigen recognition depends on detection of antigen by special receptors. • Antigen recognition depends on cellular cooperation. • Cellular cooperation is controlled by recognition of MHC-encoded receptors.

  3. Clonal Selection Theory(F. Macfarlane Burnet) • pre-existence of of many different potential antibody producing cells • each cell displays surface receptors for specific antigens • antigen encounter selects cells • What prevents recognition/destruction of self tissues?

  4. Postulates of the Clonal Selection Hypothesis • Each lymphocyte bears a single type of receptor of a unique specificity • Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation • The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived • Lymphocytes bearing receptors specific for self molecules are deleted at an early stage in lymphocyte development and are therefore absent from the repertoire

  5. Diversity of Lymphocyte Antigen Receptors • Variable region of antigen receptor encoded by sets of gene segments • During lymphocyte development somatic gene rearrangement create unique combinations of gene segments • Once recombinant events have occurred, further rearrangement is prohibited • Receptor specificity of a lymphocyte cannot change • Each lymphocyte bears many copies of the unique receptor • At least 108 different lymphocytes in an individual

  6. Genomic Organization of heavy- and light-chain segments

  7. Development of the Antibody Repertoire • The antibody repertoire is generated during B cell development by DNA rearrangements that combine and assemble variable-region gene segments (somatic diversification theory) • Diversity is enhanced by hypermutation in mature B cells (germline theory)

  8. Some Comments on Cluster of Differentiation/Designation (CD) Antigens • What are they? • Differentiation antigens • Expressed by cells at distinct stages of differentiation • Expressed by cells having different functions • How are they detected?

  9. Fluorescence-Activated Cell Sorting (FACS)

  10. Lymphocyte Populations • B lymphocytes • Plasma cells • T lymphocytes • Helper/Inducer (CD4) • Suppressor (CD8)

  11. T Cell Recognition of Antigen • Recognize antigen peptide fragments bound to specialize cell surface molecules on antigen-presenting cells (APC). • Molecules are encoded by major histocompatibility complex • Peptides are displayed to T cells as peptide:MHC complexes • T cell antigen receptors recognize peptide:MHC complexes • Each MHC molecule can bind numerous different peptides • Two classes of MHC molecules

  12. Major Histocompatibility Complex (MHC) Gene Products • Class I • Antigen is usually endogenous (e.g. viral proteins). • CD8+ Cytotoxic T Lymphocytes (CTLs) recognize antigen in association with class I MHC gene product on APC. • Class II Molecules • Antigen is usually extracellular. • CD4+ Helper T Lymphocytes recognize antigen in association with class II MHC gene product on APC.

  13. Cellular Cooperation and Antigen Recognition + Class II MHC- associated antigen APC Extracellular Antigen CD4+ Helper T Lymphocyte

  14. B Cell Antigen Recognition • Cell surface immunoglobulin receptor or B-cell receptor (IgM and IgD) • Antigen contact initiates B-cell activation, clonal expansion, maturation to plasma cell • Antigen receptor is identical to immunoglobulin that will ultimately be produced

  15. Cellular Cooperation antigen T B H Plasma Cells Antigen presentation to T and B cells by APC T cells elaborate cytokines to facilitate B cell proliferation and maturation Antibody secretion by plasma cells Antigen presenting cell

  16. Virgin lymphocyte pool PRIMARY RESPONSE effector cells memory cell pool SECONDARY RESPONSE effector cells memory cell pool Clonal Expansion Following Antigen Exposure

  17. The Bottom Line • In order to initiate an immune response antigen must be recognized. • Antigen recognition depends on detection of antigen by special receptors. • Antigen recognition depends on cellular cooperation. • Cellular cooperation is controlled by recognition of MHC-encoded receptors. • Antigen “drives” the process resulting in “effector” cells and “memory” cells.

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