Antigen Processing and Presentation, Self MHC Restriction

1. Antigen Processing and Presentation, Self MHC Restriction

2. What Does The B Cell Immunoglobulin (Ig) Receptor Recognize? • Proteins (conformational determinants, denatured or proteolyzed determinants) • Nucleic acids • Polysaccharides • Some lipids • Small chemicals (haptens)

3. Antigen Processing and Presentation • Fragmentation of protein into peptides • Association of peptide with an MHC molecule • Transport to cell surface for expression • Different cellular pathways for association of peptide with MHC class I and class II molecules

4. Class I MHC Pathway Peptide is presented by MHC-I to CD8 cytotoxic T cell Viral protein is made oncytoplasmic ribosomes Plasma membrane Globular viral protein - intact Peptide passes with MHC from Golgi body to surface Proteasome degrades protein to peptides rER Peptide associates with MHC-I complex Peptide transporter protein moves peptide into ER MHC class I alpha and beta proteins are made on the rER Peptide with MHC goes to Golgi body Golgi body

5. Peptide MHC-II complex is presented to CD4 helper T cell Class II MHC Pathway Globular protein CD4 helper T cell Plasma membrane Fusion of endosome and exocytic vesicle Endosome Endosome fuses with plasma membrane Endocytosis Immunodominant peptide binds to class II MHC Lysosome Exocytic vesicle fuses with endosome releasing Ii from αβ dimer Protein is processed to peptides in endosome or lysosome Golgi body Class II MHC Synthesis 3 chains: α,β and Ii α β Ii Endoplasmic reticulum

7. α1 NH2 NH2 Alloantigenic sites β2 NH2 α2 COOH CHO α3 Disulfide bridge Papain cleavage Plasma membrane OH P Cytoplasm COOH Structure of Class I MHC

8. NH2 NH2 α1 β1 CHO CHO α2 β2 CHO Plasma membrane Cytoplasm COOH COOH Structure of Class II MHC

9. Points Concerning Antigen Processing and Presentation 1. Location of pathogen • viruses in cytosol, MHC class I pathway, Tc response • extracellular bacteria, MHC class II pathway, TH2 response, Ab formation • intracellular bacteria, MHC class II pathway, TH1 response

10. Points Concerning Antigen Processing and Presentation • Peptides derived from both self and non-self proteins can associate with MHC class I and class II molecules. • Chemical nature of MHC groove determines which peptides it will bind.

11. Aspects of MHC • MHC molecules are membrane-bound. Recognition by T cells requires cell-cell contact. • Peptide from cytosol associates with class I MHC and is recognized by Tc cells. Peptide from vesicles associates with class II MHC and is recognized by TH cells.

12. Aspects of MHC (continued) • Although there is a high degree of polymorphism for a species, an individual has maximum of six different class I MHC products and only slightly more class II MHC products. A peptide must associate with a given MHC of that individual, otherwise no immune response can occur. That is one level of control.

13. Aspects of MHC (continued) • Mature T cells must have a T cell receptor that recognizes the peptide associated with MHC. This is the second level of control. • Each MHC molecule has only one binding site. The different peptides a given MHC molecule can bind all types to the same site, but only one at a time.

14. Animation oh MHC I & II

15. Lymphatic Tissues Primary Lymph Tissues Secondary Lymph Tissues Bone Marrow Thymus Gland Spleen Lymph Nodes Bayer’s Patches Bursa of Fabrices

17. Types of Abs Against Same Ag Allotype Idiotype Isotype Different classes IgG, IgM, IgA IgD, IgE Different Variable For the same Ag On Same Class Different Amimals e.g.: Horse to Human