BIO444 MHC Processing
MHC & Antigen Presentation - Chapter 3
Page 1
Introduction to MHC and Antigen Presentation
Page 2: Immune System Receptors & Ligands
Innate Immune System
PRRs (Pattern Recognition Receptors) recognize PAMPs (Pathogen-Associated Molecular Patterns) and DAMPs (Damage-Associated Molecular Patterns).
Adaptive Immune System
Lymphocyte receptors (B & T cell receptors) recognize specific antigens.
Page 3: Antigens
Definition of Antigen
Any substance that triggers an adaptive immune response.
Page 4: Adaptive Immune Receptors
Types of Receptors on Lymphocytes
T-cell receptor (TCR)
B-cell receptor (BCR)
Page 5: T Cell Receptor
Functionality of T Cells
T cells locate and react rapidly to antigens.
Page 6: T Cell Receptor
Recognition Mechanism
T cells recognize protein fragments (short amino acid sequences).
Cannot directly recognize or be activated by free antigens on pathogens.
Page 7: Antigen Presentation
Process of Antigen Presentation
Cells present protein fragments to T cells using MHC proteins.
Page 8: T-Cell Receptors (TCR)
Recognition Specificity
T cells recognize peptides displayed on antigen-presenting cells (APCs) bound to MHC molecules.
Ensures T cells do not interact with free antigens.
Page 9: Major Histocompatibility Complex (MHC)
Role of MHC in Antigen Presentation
MHC molecules are membrane glycoproteins that display peptide antigens for T lymphocyte recognition.
Also known as human leukocyte antigens (HLAs).
Approximately 10,000 MHC molecules on the surface of an APC.
Page 10: Major Histocompatibility Complex (MHC)
Classes of MHC Proteins
MHC Class I
MHC Class II
Page 11: Structure of MHC Molecules
Peptide-Binding Clefts
MHC Class I: accommodates peptides 8 to 10 amino acids long.
MHC Class II: accommodates peptides 10 to 30 amino acids long.
Page 12: Peptide Binding Groove of MHC Class I
Specifics of MHC Class I
Accommodates peptides 8-9 amino acids long.
Page 13: MHC Class I and II
Peptide Lengths
MHC Class I: 8-10 amino acids.
MHC Class II: variable length (10-30 amino acids).
Page 14: TCR Antigen Recognition
Interaction Specificity
Each TCR interacts with 1 to 3 amino acid residues of the MHC-associated peptide.
Page 15: MHC Genes
Classes of MHC Genes
Class I MHC genes
Class II MHC genes
Class III MHC genes (complement and inflammation proteins).
Page 16: MHC Genes
HLA Alleles
Most individuals have 12 different HLA alleles.
Six class I HLA alleles and six or seven class II alleles.
Page 17: MHC Genes
Polymorphism
MHC genes are highly polymorphic, with many different alleles present in the population.
Page 18: Major Histocompatibility Complex
Graft Rejection
MHC genes contribute significantly to graft rejection.
Over 14,000 alleles, with a variety of class I and class II molecules.
Page 19: MHC Gene Family
Polymorphism in Peptide-Binding Region
Different MHC variants bind different peptide lengths.
Ensures diverse peptide presentation across the population.
Page 20: Inheritance of MHC Genes
Co-Dominant Expression
Alleles from both parents are expressed equally.
Maximizes the diversity of MHC proteins.
Page 21: MHC Genes
Inheritance Patterns
Siblings have a 1 in 4 chance of inheriting the same MHC alleles.
Page 22: Types of T Cells
Major Types of T Cells
CD4+ T cells (T helper cells)
CD8+ T cells (T cytotoxic cells)
Page 23: MHC Class I
Expression and Function
Expressed on all nucleated cells, except mature red blood cells.
Presents intracellular antigen peptides to CD8+ T cells.
Page 24: Proteasomes
Peptide Generation
Proteins are tagged for degradation by ubiquitin and processed by proteasomes.
Page 25: Antigen Processing
Class I MHC Processing
Proteins in the cytosol are processed and displayed by class I MHC molecules.
Page 26: Proteasomes
Specialized Proteasomes
Professional APCs have immunoproteasomes for specific peptide generation.
Page 27: Cytosolic Antigens
Processing for Class I MHC
Peptides are transported to the rough endoplasmic reticulum for loading onto MHC class I.
Page 28: MHC Class I – Peptide Loading
TAP Protein Complex
Delivers cytosolic peptides into the endoplasmic reticulum for binding to MHC class I.
Page 29: MHC Class II
Expression
Found only on dendritic cells, macrophages, and B cells.
Page 30: MHC Class II
Functionality
Presents extracellular antigen peptides to CD4+ T cells.
Page 31: MHC Class II Antigen Processing
Internalization of Antigens
APCs ingest extracellular microbes, which are processed in endosomes and lysosomes.
Page 32: Summary
TCR Recognition
TCRs recognize processed amino acid fragments presented in MHC molecules.
Dendritic cells are essential for T cell priming.
Page 33: Reading Chapter 3
**Conclusion