MHC Class II Antigen Processing MHC class II molecules are synthesized in the ER and contain an Invariant Chain to maintain their correct structure. The invariant chain also prevents endogenous self antigens from binding to the peptide groove while they are being transported to the endosome. The Invariant Chain is cleaved in the late endosome and only a Clip protein remains Abbas & Lichtman’s Basic Immunology 3-11

MHC Class II Antigen Processing Combination of exocytic vesicle containing newly synthesized MHC class II with vesicle containing microbial peptides. Microbial protein replaces the Clip protein in the protein binding groove a process called “peptide exchange”. Abbas & Lichtman’s Basic Immunology 3-11

MHC Class II Antigen Processing Microbial peptide-MHC class II complexes are transported to the surface of the cell to be recognized by CD 4+ T cells. Abbas & Lichtman’s Basic Immunology 3-11

MHC Binding to Peptides Each MHC molecule displays one peptide at a time. MHC molecules only bind peptides. Not lipids, sugars, nucleic acids, or whole proteins. Peptides which bind to the same MHC molecule share features at the aa level.

MHC Binding to Peptides Only MHC molecules with peptides are expressed by antigen presenting cells. “empty” MHC molecules are degraded inside the cell. Peptides bind to MHC molecules with low affinity. Slow rate of binding. Very slow rate of releasing. Many different peptides can bind to a specific MHC molecule.

How does the Immune System Handle Intracellular Pathogens? Progeny virus Virus Typical virus replication cycle: Has both extracellular phase and intracellular phase of life cycle. mRNA

How does the Immune System Handle Intracellular Pathogens? It is a job of the T lymphocyte system to recognize intracellular antigens. Intracellular antigens include: pathogens such as viruses and some bacteria tumor proteins cytoplasmic and nuclear proteins Intracellular antigens are processed and presented to CD8+ T lymphocytes in MHC class I molecules

MHC Class I Structure 1 chain a chain containing the antigen binding site. a3 domain has binding site for CD8. b2-Microglobulin Must be associated with a chain for MHC class I molecule to be expressed. 8-11aa a2 a1 a3 b2-Microglobulin Cell membrane

MHC Class I MHC class I is expressed on all nucleated cells. Only present antigen to CD8+ T cells. Abbas & Lichtman’s Basic Immunology 3-11

MHC Class I Antigen Processing Microbial protein is degraded in the cytoplasm into peptides. Tagged by a protein called Ubiquitin Degraded in proteosomes (tunnel of degradation enzymes) Result in peptide fragments 8-11 aa long Abbas & Lichtman’s Basic Immunology 3-11

MHC Class I Antigen Processing Microbial peptides are transported into the ER where they can bind newly synthesized class I MHC molecules. Transporter molecules called TAP-1 and TAP-2 are responsible for transport of peptides into ER Peptides bind to peptide binding cleft of MHC class I molecules Abbas & Lichtman’s Basic Immunology 3-11