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Antigens

Explore the factors influencing immunogenicity, the distinction between antigens and immunogens, and the role of epitopes. Learn how haptens, mitogens, and adjuvants affect immune responses.

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Antigens

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  1. Antigens Hugh B. Fackrell

  2. Assigned Reading • Content Outline • Performance Objectives • Key terms • Key Concepts • Short Answer Questions

  3. ASSIGNED READING • Chapter 4 pp 87-106

  4. Immunogenicity vs antigenicity Factors that influence immunogenicity immunogen contributions biological system contributions Epitopes B cell epitopes T cell epitopes Haptens Mitogens OUTLINE

  5. Definitions • Antigen- a substance recognized by T and B cell receptors • Immunogen - a substance capable of eliciting immune response • Hapten - a substance of low molecular weight, that can bind antibodies but induce response only if covalently attached to large carrier Klein, 1992

  6. Definitions (cont) • Antigenic Determinant: Specific sequence of amino acids that combine with receptor • Epitope:an antigenic determinant on the surface of a molecule • Cryotope:An antigenic determinant that is buried within a molecule and thus is unavailable in the intact molecule

  7. Immunogen vs Antigen • Immunogen • Any compound that triggers the immune response • Antigen • Any compound that combines with the products of an immune response

  8. Factors Influencing Immunogenicity • immunogen contributions • biological system contributions

  9. Immunogen Contributions • Chemical nature • Chemical complexity • Molecular size • Conformation • Foreigness

  10. Effects of Biological System on Immunogenicity • Genotype • Dose of Immunogen • Route of Injection • Adjuvants

  11. Genotypic Influences • Immune Responsiveness • Some strains of inbred mice respond to specific immunogen (high responders) • Other strains do not (low responders) • Hybrids of above have intermediate response • Structure of MHC receptors on cell membrane

  12. MHC Receptors

  13. Dose of Immunogen • Tolerance: Specific non response to an immunogen • Dose dependent • Too low- no effect • Low dose: Tolerize T cell • High dose: Tolerize B cells

  14. 200- 100- % Response 0- log [antigen injected] Mitcheson Tolerance Exp Immunity Low Zone Tolerance High Zone Tolerance

  15. Tolerogenic vs Immunogenic • Immunogenicity • antigens first processed by APC • APC reacts with lymphocyte • response • Tolerogenicity • antigens react directly with lymphocyte • NO response Immunogenicity requires co stimulation

  16. Route of Injection • Parenteral injection • other than digestive tract • intravenous, intradermal, sucutaneous, intramuscular, intraperitioneal • Exposure to different lymphocyte populations • intravenous - spleen • subcutaneous- lymph nodes

  17. Adjuvants • Substances that enhance immunogenicity of an antigen • alum • Freund’s ( contains Mycobacterium) • Mechanisms • prolong life of antigen • enhance co-stimulatory signals • nonspecific multiplication of lymphocyte • granuloma formation

  18. Haptens • Antigenic but not immunogenic • small molecules eg DiNitroPhenol • Flexible molecules eg gelatin • When linked to acarriermolecule becomes immunogenic • Hapten- Carrier conjugates • Hapten immunodominant determinant

  19. Epitopes • Size • Specificity • Affinity

  20. Construction of Epitope • Continuous • stretch of contiguous residues endowed with distinctive conformational features • Discontinous • group of residues that are non contiguous in the sequence but are brought together by the folding of the polypeptide chain • Klein 1992

  21. B cell Epitopes

  22. Immunoglobulin: B cell receptor

  23. Antigen - Antibody binding • Hydrogen bonds • Electrostatic forces • Van der Walls interactions • Hydrophobic interactions

  24. T cell Epitopes

  25. Mitogens

  26. The End

  27. Molecular Dissection ofProteinaceous Antigens Created Maria Sawicki Updated Hugh B. Fackrell Dec 1997

  28. X - Ray Crystallography • Crystallized Antigen or Antigen - Antibody Complex • Electron Density Map of the Molecule • Three Dimensional Images

  29. Construction of Epitope • Continuous • stretch of contiguous residues endowed with distinctive conformational features • Discontinous • group of residues that are non contiguous in the sequence but are brought together by the folding of the polypeptide chain • Klein 1992

  30. ANTIGEN RECOGNITION SYSTEMS • Immunoglobulins • intact antigen is presented with several conformational epitopes • T cell receptors • “processed antigen” is presented and can be recognized only in complex with Major HIstocompability Complex .

  31. Synthetic Peptides • Overlapping Epitopes • Immunodominance Benjamini ,1984

  32. Prediction of antigenicity • Region accesibility • Novotny 1988 • Segmental mobility • Westhof et al 1984, Tainer et al 1985 • Relative hydrophilicity • Hoop and Woods1983, Hoop 1986 • Chain termination • Thorton and Sibanda 1983 • Segmental variability • Jemmerson and Parerson 1985

  33. Epitope MappingCross-reactivity studies Native Protein and Peptide Fragments Synthetic Peptides Closely Related Proteins • Van Renmortel, 1988

  34. Studies of Native Proteins and Peptide Fragments • Conformational influences • Native protein derivatives • Overlapping peptide sequences • Derivatives of active peptides • Synthetic peptides Atassi, 1978

  35. The End

  36. Performance Objectives Key terms, concepts short answers

  37. KEY TERMS • Accessibility, antigen, antigenic determinants, antigenic site mobility, • antigenicity, continous (linear) determinants), discontinous (conformational) determinants • epitopes, agreotopes, haptens, immunodominance, immunogen, immunogenicity

  38. KEY CONCEPTS • Differentiate between and antigen's inductive and reactive abilities. • Explain the factors that bestow immunogenicity on molecules • Describe the discrete and distinctive sites on and antigen that are recognized by a B cell Immunoglobulin

  39. KEY CONCEPTS • Describe the discrete and distinctive sites on and antigen that are recognized by a T cell receptor • Describe the discrete and distinctive sites on and antigen that are recognized by the Major Histocompatability Complex • Discuss some important characteristics of protein antigenic determinants

  40. SHORT ANSWER QUESTIONS

  41. Differentiate between immunogenicity and antigenicity. • All immunogens are antigens but all antigens are not immunogens. Explain with the use of specific examples. • An entire microbe or molecule does not induce and immune response. Explain. • Irrespective of the number of epitopes that a molecule has, the immune response is biased and sees what it wants to see. Explain.

  42. Haptens are usually coupled to a carrier molecule before they are immunogenic. How can you demonstrate that the selected immunoglobulins are specific for the hapten and not for the carrier? • As a corollory, would you expect ALL of the antibodies to be specific for the hapten? explain.

  43. Why is the definition of an antigen considered to be an operational definition. • Differentiate between epitopes and agreotopes. • Differentiate between epitopes recognized by B cell receptor and epitopes recognized by T cell receptors.

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