Antigen Processing and Presentation, Self MHC Restriction

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

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

Proteasome degrades protein to protein moves peptide into ER Class I MHC Pathway Peptide is presented by MHC-I to CD8 cytotoxic T cell Viral protein is made on cytoplasmic 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 Golgi body Peptide with MHC goes to Golgi body

Class II MHC Pathway Plasma membrane Peptide MHC-II complex is presented to CD4 helper T cell CD4 helper T cell Globular protein 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

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

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

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

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.

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.

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.

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.

Animation oh MHC I & II

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

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