Antigen Presentation and

Recognition by Lymphocytes

Sabha Rabaya
PTUK
 Learning Objectives:

By the end of this lecture, students should be able

to:
1.Describe the process of antigen presentation.
2.Distinguish between the roles of major
histocompatibility complex (MHC) class I and
class II molecules.
3.Explain how lymphocytes recognize antigens
via their specific receptors.
4.Discuss the role of co-stimulatory signals in
lymphocyte activation.
 Introduction to Antigen Presentation

• Antigen presentation is a crucial

process in the adaptive immune
response, allowing lymphocytes to
recognize and respond to
pathogens.
• Specialized cells, called antigen-
presenting cells (APCs), capture
antigens and display them on their
surface bound to MHC molecules,
facilitating recognition by T
lymphocytes.
 Introduction to Antigen Presentation
• Adaptive immune responses are initiated by the recognition of
antigens by antigen receptors of lymphocytes.

• B and T lymphocytes differ in the types of antigens they recognize.

• The antigen receptors of B lymphocytes— namely, membrane-bound

antibodies—can recognize a variety of macromolecules (proteins,
polysaccharides, lipids, nucleic acids), in soluble form or cell surface–
associated form, as well as small chemicals. Therefore, B cell–mediated
humoral immune responses may be generated against many types of
microbial cell wall and soluble antigens.
 Introduction to Antigen Presentation
• Most T lymphocytes have antigen receptors that can see only peptide
fragments of protein antigens, and only when these peptides are
displayed on host cell surfaces bound to specialized proteins called
major histocompatibility complex (MHC) molecules.

• Because the association of antigenic peptides and MHC molecules

occurs inside cells, T cell– mediated immune responses may be
generated only against protein antigens that are either produced in or
taken up by host cells.
 Introduction to Antigen Presentation
• CD4+ and CD8+ T cells can see peptides only when these peptides are
displayed by that individual’s MHC molecules. This property of T cells is
called MHC restriction

• Some small populations of T cells recognize lipid and other nonpeptide

antigens either presented by nonpolymorphic class I MHC–like
molecules or without a requirement for a specialized antigen display
system.
MHC: Background
 Introduction to Antigen Presentation
• Key Concepts:
Antigen: A molecule capable of inducing an immune
response.
APCs: Include dendritic cells, macrophages, and B cells.
MHC Molecules: Proteins that present antigens on cell
surfaces, classified into two types:
◘MHC Class I: Found on all nucleated cells; presents
endogenous antigens.
◘MHC Class II: Expressed mainly on professional APCs;
presents exogenous antigens.
 Structure and Function of Major Histocompatibility
Complex Molecules
• MHC molecules are membrane proteins on APCs that display peptide
antigens for recognition by T lymphocytes.

• The MHC molecules are encoded in a large cluster of genes located on

chromosome 6.

• They were first identified by their potent effect on the immune

response to transplanted tissue (see later). For that reason, the gene
complex was termed the ‘‘major histocompatibility complex.’’

• In humans, these genes are often called human leukocyte antigens

(HLA), as they were first discovered through antigenic differences
between white blood cells from different individuals.

• MHC is the term for the region located on the short arm of
chromosome 6p21.31 in humans. It contains more than 200 genes.
 MHC: Background

Genetic map of the MHC regions.

https://www.immunopaedia.org.za/immun
10 ology/basics/4-mhc-antigen-
presentation/?print=pdf
 Structure and Function of Major Histocompatibility
Complex Molecules

• MHC molecules were first discovered as proteins encoded by the

murine MHC locus involved in graft rejection. They were rediscovered in
humans when it was found that women who had multiple pregnancies,
or recipients of multiple blood transfusions, made antibodies that
recognized proteins on the white blood cells (leukocytes) of paternal or
donor origin, respectively. These proteins were called human leukocyte
antigens (HLAs) and were soon shown to be analogous to the MHC
molecules identified in mice.
 MHC: Background
• The principal function of the MHC is to present antigen to T cells to
discriminate between self (our cells and tissues) and nonself (the
invaders or modified self).

• Two main characteristics of the MHC make it difficult for pathogens

to evade immune responses:

First, the MHC is polygenic. It contains several different MHC-I and

MHC-II genes so that every individual possesses a set of MHC
molecules with different ranges of peptide-binding specificities.

Second, the MHC is extremely polymorphic. The MHC genes display

the greatest degree of polymorphism in the human genome. There
are multiple variants of each gene within the population as a
whole. The different variants that are inherited by an individual
from a parent are known as alleles.
 Structure and Function of Major Histocompatibility
Complex Molecules
• In all vertebrates, the MHC contains two sets of highly polymorphic
genes, called the class I and class II MHC genes.

•Class I and class II MHC molecules are membrane proteins that each
contains an extracellular peptide- binding cleft. Although the two
classes of molecules differ in subunit composition, they are very similar
in overall structure
 CAPTURE OF PROTEIN ANTIGENS BY ANTIGEN-
PRESENTING CELLS
• Protein antigens of microbes that enter the body are captured mainly
by dendritic cells and concentrated in the peripheral (secondary)
lymphoid organs, where immune responses are initiated

• Antigens are taken to peripheral lymphoid organs in two ways.

◘ Microbes or their antigens may enter the lymph or blood and
circulate to lymph nodes or spleen, respectively, where they are
captured by resident dendritic cells and presented to T cells. Other
APCs may also capture antigens and display them to B cells in these
organs.

◘ Dendritic cells in epithelia, connective tissues, and organs transport

microbial antigens to lymphoid organs. This process involves a series
of events following the encounter of dendritic cells with microbes—
capture of antigens, activation of the dendritic cells, migration of
the antigen-carrying cells to lymph nodes, and display of the antigen
to T cells
 Dendritic Cells
• The epithelia and subepithelial tissues contain a network of cells with
long processes, called dendritic cells; these cells are also present in
the T cell–rich areas of peripheral lymphoid organs and, in smaller
numbers, in most other organs

• There are two major populations of dendritic cells called

◘ conventional (or classical)
•Majority of dendritic cells in tissues and lymphoid organs

◘ Plasmacytoid
• Plasmacytoid dendritic cells are named because of their morphologic
resemblance to plasma cells; they are present in the blood and tissues.
Plasmacytoid dendritic cells are also the major source of type I
interferons in innate immune responses to viral infections
 Dendritic Cells
1. Antigen Capture by Dendritic Cells
Receptors Used: Dendritic cells use membrane receptors like cell
surface lectins to bind microbial carbohydrates.
Uptake Mechanisms: Antigens are internalized via phagocytosis or
receptor mediated endocytosis.

2. At the same time, Innate Immune Activation

Pattern Recognition: Microbial products bind to Toll-like receptors
(TLRs) and other innate receptors.
Cytokine Production: Results in inflammatory cytokines such as TNF
and IL-1. The combination of innate receptor signaling and cytokines
activates the dendritic cells
 Dendritic Cells
3. Dendritic Cell Activation and Migration
Phenotypic Changes: Activation leads to reduced adhesion to
epithelia.
Migration: Chemokines guide dendritic cells to lymph nodes via
lymphatic vessels.
Maturation: Transition from antigen-capturing cells to antigen-
presenting cells (APCs).
4. Role in T Cell Activation
Antigen Presentation: Mature dendritic cells express MHC molecules
and costimulators to activate T cells.
Efficient Response: Microbial antigens in lymph nodes initiate T cell
responses within 12–18 hours.
 Other APCs

Dendritic Cells: Primary inducers of T-dependent responses,

especially for naive T cells.
Macrophages: Present antigens to effector T cells in cell-
mediated immune responses.
B Lymphocytes: Present protein antigens to helper T cells for
humoral immune responses.
Nucleated Cells: any nucleated cell containing foreign
(microbial or tumor) protein antigens in the cytosol can
present peptides derivedfrom these antigens to CD8+ T cells.
 Processing and Presentation of Protein
Antigens

Proteins in the cytosol of any nucleated cell are

processed in proteolytic complexes called proteasomes
and displayed by class I MHC molecules,
whereas extracellular proteins that are internalized
by specialized APCs (dendritic cells, macrophages,
B cells) are processed in late endosomes
and lysosomes and displayed by class II MHC molecules.
 Processing and Presentation of Protein Antigens
MHC Class I Pathway (Endogenous Pathway):
Antigen Source: Proteins enter the cytoplasm of cells either from
endogenous synthesis by microbes, such as viruses, that reside in the
cytosol of infected cells or from microbes that are ingested but
whose antigens are transported into the cytosol.
mutated or altered host genes that encode cytosolic or nuclear
proteins, as in tumors
Processing:
•Proteins are degraded into peptides by the proteasome.
•Peptides are transported into the endoplasmic reticulum (ER) by
the transporter associated with antigen processing (TAP).
Presentation:
•Peptides are loaded onto MHC class I molecules in the ER.
•The MHC-peptide complex is transported to the cell surface.
Recognition:
• Recognized by CD8+ cytotoxic T cells.
 Processing and Presentation of Protein Antigens
MHC Class II Pathway (Exogenous Pathway):
Antigen Source: Extracellular pathogens (e.g., bacteria) or soluble
proteins.
Processing:
•Antigens are internalized via phagocytosis or endocytosis.
•Proteins are degraded in acidic endosomal/lysosomal
compartments.
Presentation:
• Peptides are loaded onto MHC class II molecules within
endosomes.
The MHC-peptide complex is transported to the cell surface.
Recognition:
Recognized by CD4+ helper T cells.
Role of MHC-associated antigen presentation in recognition of
microbial antigens by CD8+ and CD4+ effector T cells