Antigen Presentation Fundamentals I for Dentistry & Optometry Textbook: Medical Microbiology, 6 th Edition, Murray Chapter 11 Jim Collawn, MCLM

Study Objectives 1.Compare and contrast class I and class II MHC- restricted responses with regard to A. source of antigens B. antigen processing requirements C. role of chaperones D. types of T cell involved 2.Discuss the invariant chain’s role in the demarcation between class I and class II MHC- restricted responses. 3.Discuss HLA-DM’s possible role in antigen processing.

Humoral and Cell- mediated Immune Responses

Major Players in T cell Responses

T lymphocyte and Macrophage (right)

Types of T cells 1.Cytotoxic T cells (CTLs) A.Kill virally infected cells B.Kill cells containing cytosolic bacteria C.Kill tumor cells 2.Inflammatory T cells (T H 1) A.Activate macrophages to kill intracellular bacteria 3.Helper T cells (T H 2) A.Activate B cells to make antibody

Schematic Diagrams of MHC class I and class II Molecules

MHC class I (top view)

Major Histocompatibility Complex

HLA-DR1 (blue) and HLA-A2

MHC class I

MHC class II

Anchor Residues for MHC class I peptides

Conformation of Peptides Bound to MHC class I

Solvent-accessible Area of H-2K b

Anchor Residues for MHC class II peptides

Antigen Processing is Necessary for Helper T cell Activation

Antigen-presenting Cells (MHC Class II-positive cells) HLA-DR, HLA-DP, HLA-DQ

Target Cells (MHC Class I-positive cells) HLA-A, HLA-B, HLA-C All nucleated cells

Degradation of Intracellular Proteins

Transporter associated with Antigen Processing

Generation of Peptide-class I MHC Complexes

Demarcation between MHC class I and class II Processing Pathways

Cytosolic and Endocytic Pathways for Antigen Processing

Assembly of MHC class II Molecules

Study Objectives 1.Compare and contrast class I and class II MHC- restricted responses with regard to A. source of antigens B. antigen processing requirements C. role of chaperones D. types of T cell involved 2.Discuss the invariant chain’s role in the demarcation between class I and class II MHC- restricted responses. 3.Discuss HLA-DM’s possible role in antigen processing.

Sample Questions The MHC class II molecule –is associated with ß-2 microglobulin. –binds peptide antigens from the endogenous pathway. –is associated with the invariant chain. –is expressed on all cell types. Exogenous antigens –are taken up by cells through endocytosis or phagocytosis. –are bound to MHC class I molecules. –are processed by the proteasome. –become associated with MHC class I molecules in the endoplasmic reticulum.

Sample Questions HLA-DR –presents antigens to cytotoxic T cells. –is a chaperone that facilitates CLIP removal and peptide binding. –is an MHC class II molecule. –binds to endogenous antigens. The proteolytic activity necessary for the generation of MHC class II- associated peptides is provided by –the proteasome. –the lysosome. –furin. –the endoplasmic reticulum.