Lecture 4: Antigen Processing and

Presentation
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IMMC
 Objectives

▪ Compare the structure and expression of MHC class I and II (proteins).

▪ Describe the role MHC in regulating the immune response.
▪ Discuss the source and types of antigen processed by class I and II
molecules.
▪ List professional antigen presenting cells.
▪ Discuss the role of the T helper cell in both cell-mediated and humoral
immunity.
 Introduction

▪ Antigen Recognition by T and B cells:

▪ B cells recognize free antigens using antibodies.
▪ T cells recognize antigens as peptides presented on cell surfaces by MHC molecules.
▪ Major Histocompatibility Complex (MHC):
▪ Encoded by the MHC locus genes.
▪ Acts as a cell-surface vessel to present antigen fragments.
▪ Essential for T-cell engagement via their receptors.
▪ MHC Importance and Discovery:
▪ Named for its role in tissue transplant acceptance or rejection.
▪ 1980 Nobel Prize awarded for discoveries on MHC's role in organ transplants and immune
responses.
 Introduction

▪ Classes of MHC Molecules:

▪ Class I and II:
▪ MHC class I in human is known as HLA class I and MHC class II is known as HLA
class II.
▪ Similar shapes, present antigens to T cells but differ in roles and structure.
▪ MHC Structure, Function, and Expression:
▪ Discussion of MHC class I and II structures, genetic organization, and inheritance.
▪ Regulation of MHC gene expression and its role in immunity.
▪ Antigen Processing and Presentation:
▪ Pathways of antigen degradation, association with MHC molecules.
▪ Presentation of these complexes on cell surfaces for T-cell recognition.
▪ Includes unique pathways like cross-presentation and handling of nonpeptide antigens.
 Antigens
Capturing and Processing

▪ Cells encounter the antigens upon crossing the

physical barriers and then capture the antigens
to engulf the antigens leading to its appearance
in either in the cytosol or in a vesicle.

▪ Once a pathogen is inside a cell it needs to be

degraded into protein peptides in a sequence
event and associate with an MHC molecule.
 Antigens Presentation

▪ Once an antigen is degraded it needs to be transported to

the surface of the cell and displayed within a cleft of an
MHC molecule in order to be recognized by TCR on the T
lymphocyte.

T Cell APC
 Antigens Presentation
▪ Once an antigen is degraded it needs to be transported to the surface of the cell and displayed
within a cleft of an MHC molecule to be recognized by TCR on the T lymphocyte.

▪ List of Antigen Presenting Cells

▪ Macrophages Antigen Presenting Cells
▪ Dendritic Cells
▪ B cells
 What is Major Histocompatibility
Complex (MHC)?
▪ MHC is a set of cell surface molecules encoded by a large genetic
complex with multiple loci.

▪ The MHC loci encode 2 major classes of membrane-bound glycoprotiens:

▪ 1. MHC class I
▪ 2. MHC class II
▪ MHC function:
▪ The major function of MHC is to bind to “processed antigen peptides”
displayed on the cell surface to be recognized by specific T lymphocytes
to initiate an immune response.
 MHC Class I & II
▪ MHC Class I Molecules:
▪ Found on all nucleated cells.
▪ Present peptides derived from endogenous proteins.
▪ Interact with CD8+ T cells.
▪ MHC Class II Molecules:
▪ Expressed mainly on professional APCs (dendritic cells, macrophages, B cells).
▪ Present peptides derived from exogenous proteins.
▪ Interact with CD4+ T cells.
 Structure of MHC Class I & II
▪ MHC class I: Consist of 4 domains
▪ (1, 2, 3 and β2-microglobuline)
▪ Is only expressed on antigen presenting cells
▪ (Dendritic cells, Macrophages, B lymphocytes) MHC Class I MHC Class II
▪ And is recognized by CD4+ helper T cells (Th).
▪ MHC class II: Consist of 4 domains
▪ (1, 2, β1and β2)

▪ Is expressed on all cell types

▪ except unnucleated cells (Red Blood Cells)
▪ And is recognized by CD8+ cytotoxic T cells.
 Human Leukocyte Antigen (HLA)
▪ The Major Histocompatibility Complex in human is known as the human leukocyte
antigen (HLA). MHC class I in human is known as HLA class I and MHC class II is
known as HLA class II.
▪ HLA class I and class II are polygenic (several loci encoding products with
essentially the same function)
▪ HLA class I: HLA-A, HLA-B and HLA-C
▪ HLA class II: HLA-DR, HLA-DP and HLA-DQ
▪ HLA class I and class II are polymorphic (variability of alleles in the species)
▪ There are > 2000 HLA-A alleles , > 3000 HLA-B alleles and > 2000 HLA-C alleles.
For example HLA-A2, HLA-A26 and HLA-B50
 Types of Presented Antigens

▪ Endogenous antigens are degraded into peptides within the cytosol by

proteasomes and assembled with MHC class I.
▪ For example: viruses and tumours.

▪ Exogenous antigens are internalized and degraded within endocytic

compartments and subsequently assembled with MHC class II.
▪ For example: bacteria
 Endogenous antigens:
Processing and Presentation
▪ Process by which cells present internal, cellular proteins
to T cells.
▪ Protein Degradation:
▪ Cytosolic proteins tagged for degradation by ubiquitin.
▪ Proteasome (immunoproteasome in immune cells)
cleaves proteins into peptide fragments.
▪ Peptide Transport:
▪ Peptides transported from cytosol to Endoplasmic
reticulum (ER) by transporters associated with antigen
processing (TAP) molecules.
▪ TAP preference for peptides 8-10 amino acids in length.
▪ Then they get loaded into MHC class I and transported to
the surface of the cell.

Kuby Immunology (8th ed)

 Endogenous antigens:
Processing and Presentation
▪ MHC Class I Loading:
▪ In the ER, peptide fragments bind to
newly synthesized MHC Class I
molecules.
▪ The peptide-MHC Class I complex is
stabilized by the addition of β2-
microglobulin.
▪ Transport and Expression on Cell
Surface:
▪ Complexes are transported to the
Golgi apparatus, then to the cell
surface.
▪ Presented antigens are now available
for recognition by CD8+ T cells.
 Exogenous Antigens:
Processing and Presentation

▪ Process by which cells present external, non-cellular proteins to T cells.

▪ Antigen Uptake:
▪ Antigens are internalized through phagocytosis or endocytosis.
▪ Encapsulated in vesicles that fuse with lysosomes.
▪ Antigen Processing:
▪ In lysosomes, antigens are degraded into peptide fragments.
▪ Acidic environment and lysosomal enzymes facilitate the breakdown.
 Exogenous Antigens:
Processing and Presentation
➢ MHC Class II Loading:
➢ MHC Class II molecules synthesized in ER with an invariant chain that blocks the peptide-
binding groove.
➢ In endosomes, invariant chain is cleaved, leaving Class II-associated invariant chain
peptide (CLIP) in the groove.

➢ Peptide-MHC Class II Complex Formation:

➢ CLIP is removed and peptides bind to the MHC Class II molecules.
➢ The stable peptide-MHC Class II complexes are transported to the cell surface.
 Exogenous Antigens:
Processing and Presentation

Endosome
containing degraded Peptides binds to
protein (i.e., MHC class II. MHC
peptides) fuses with class II + peptide are
endosome displayed on the cell
containing MHC surface
class II
 MHC Restriction
▪ Phenomenon where T cells recognize antigenic
peptides only when presented in conjunction with
MHC molecules.
▪ T Cell Recognition:
▪ T cell receptors (TCRs) are designed to
recognize a complex of peptide and MHC
molecule, not peptide alone.
▪ Specificity towards MHC-peptide complexes
ensures that T cells can effectively monitor
cellular processes.
▪ Role in Immune Response:
▪ Ensures that T cells only respond to peptides
displayed on self-MHC molecules, crucial for
distinguishing self from non-self.
▪ Central to the immune system's ability to
target infected or dysfunctional cells without
harming normal body cells.
 Clinical Relevance
▪ Transplantation Compatibility:
▪ MHC molecules are major determinants in organ and tissue transplant compatibility.
▪ Mismatches in MHC can lead to transplant rejection.

▪ Autoimmune Diseases:
▪ Certain MHC genotypes are associated with higher risks for autoimmune diseases like Type 1 diabetes and
rheumatoid arthritis.

▪ Infectious Diseases:
▪ MHC diversity influences susceptibility to infections and the outcome of diseases like HIV and malaria.

▪ Cancer Immunotherapy:
▪ Understanding MHC involvement in presenting tumor antigens can enhance the effectiveness of cancer
vaccines and adoptive T cell therapies.

▪ Personalized Medicine:
▪ MHC profiling can guide personalized medicine approaches, tailoring treatments based on individual MHC
makeup to enhance efficacy and reduce adverse effects .
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Thank you
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