Display and Recognition of Antigens

Slide 1 · Display and Recognition of Antigens

Normal immune response: mechanisms and clinical correlation

Peripheral antigen

Dendritic cell

Naive lymphocyte

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain antigen concentration in secondary lymphoid organs.

Compare MHC I/CD8 and MHC II/CD4 presentation pathways.

Distinguish TCR recognition of peptide–MHC from BCR recognition of native antigen.

Explain how innate sensing, B7–CD28 costimulation, and tolerance modify recognition.

Slide 3 · The immune system faces a sampling problem

Microbes and foreign antigens can enter through many anatomic sites.

An individual antigen-specific naive lymphocyte is too rare to inspect every site.

The solution is concentrating captured antigens where recirculating lymphocytes can encounter them.

Distributed portals

Antigen collection

Secondary lymphoid organ

Lymphocyte encounter

Slide 4 · Secondary lymphoid organs concentrate antigens

Antigens and presenting cells accumulate in regional lymphoid tissues.

Naive lymphocytes continually pass through these sites.

Spatial concentration raises the probability of productive recognition.

Tissue antigen

Lymphoid concentration

Naive cell surveillance

Slide 5 · Epithelial surfaces are common portals of entry

Microbes frequently arrive at epithelial barriers.

Dendritic cells reside under epithelia and in tissue interstitia.

These locations make DCs well placed to acquire foreign protein antigens.

Epithelial entry

Tissue antigen

Resident DC

Slide 6 · Dendritic cells capture microbial antigens

Dendritic cells possess receptors for microbial structures, including TLRs and lectins.

They collect antigens in peripheral tissues.

Antigen acquisition precedes presentation to naive T cells.

Microbial antigen

DC uptake

Processing

Presentation

Slide 7 · Migrating DCs transport antigenic cargo

DCs carrying microbial antigens travel from tissues through lymphatic vessels.

The destination is the draining lymph node.

This physically links a peripheral infection with an organized T-cell encounter site.

Peripheral

Tissue

DC

Afferent

Lymphatic

Draining

Lymph node

DC

Migration conveys antigen toward naive T cells

Slide 8 · Lymph nodes specialize in tissue-derived antigens

Lymph draining tissues reaches lymph nodes along lymphatic channels.

Antigens and antigen-loaded DCs become concentrated in these organs.

Lymph nodes are key initiation sites for adaptive responses to tissue-entry microbes.

Tissue

Lymphatic route

Lymph node

Adaptive response

Slide 9 · Naive lymphocytes recirculate through lymphoid organs

Naive lymphocytes search repeatedly through secondary lymphoid tissues.

Antigen concentration converts a rare receptor–ligand encounter into a feasible event.

Circulation and antigen transport solve complementary parts of the surveillance problem.

Antigen delivered to node < Naive cell

Arrives through circulation

Slide 10 · Recognition happens in the correct tissue compartment

Naive T cells encounter antigen-presenting DCs in T-cell zones of nodes.

B cells are concentrated in follicles that support humoral responses.

Regional organization brings each lymphocyte type into contact with its appropriate antigen display.

DC in paracortex

Naive T cell

Activated T-cell response

Slide 11 · MHC molecules display peptide fragments

Major histocompatibility complex proteins bind peptides derived from proteins.

A peptide–MHC complex appears at the cell surface for T-cell scrutiny.

The antigenic unit recognized by most conventional T cells is peptide plus MHC, not free protein.

Protein antigen

Peptide fragment

MHC display

Slide 12 · Processing precedes classical T-cell recognition

Protein antigens are degraded into peptide fragments.

Peptides associate with MHC proteins inside appropriate cellular compartments.

Loaded complexes travel to or remain at the plasma membrane for T-cell recognition.

Protein

Proteolysis

Peptide–MHC

Surface display

Slide 13 · HLA is the human MHC system

The human major histocompatibility complex is called HLA.

HLA genes are clustered on chromosome 6.

Their products were discovered through roles in transplant compatibility.

HLA genes

Surface peptide display

T-cell recognition

Slide 14 · HLA diversity influences peptide presentation

MHC genes are highly polymorphic across humans.

Allelic differences alter which peptides can bind the MHC groove.

HLA diversity also creates a major biological barrier to organ transplantation.

HLA polymorphism

Different binding

Grooves

Different peptides

Displayed

Slide 15 · MHC class I and II divide presentation tasks

Class I primarily displays peptides from cytosolic proteins to CD8 T cells.

Class II displays peptides from internalized extracellular proteins to CD4 T cells.

The separation links antigen origin with appropriate effector-cell selection.

Cytosol → MHC I → CD8

Endosome → MHC II → CD4

Compared with

Slide 16 · MHC class I distribution supports immunosurveillance

MHC I occurs on all nucleated cells and platelets.

Viruses may infect many nucleated cell types, and tumors can arise in them.

Broad expression enables cytotoxic T cells to inspect diverse tissues.

Nucleated cell

MHC I peptide display

CD8 surveillance

Slide 17 · Class I peptides originate in the cytosol

Cytosolic proteins include viral and abnormal tumor proteins.

These proteins become substrates for peptide generation.

The resulting fragments enter the MHC class I presentation pathway.

Cytosolic protein

Proteasome peptides

MHC I display

Slide 18 · Proteasomes generate class I peptides

Cytosolic proteins are degraded in proteasomes.

Peptides produced by this degradation can enter the class I-loading pathway.

Proteasomal processing is upstream of peptide transport to the ER.

Cytosolic proteins

Proteasome

Short peptides

Slide 19 · Class I loading occurs in the ER

Peptides from the cytosol are transported into the endoplasmic reticulum.

There they associate with newly synthesized MHC I proteins.

Stable complexes subsequently reach the cell surface.

Intracellular processing

Cytosol

Proteasome peptides

ER lumen

Peptide loading onto MHC I

Cell surface

Peptide–MHC I display

Slide 20 · MHC I includes β2-microglobulin

The polymorphic MHC I heavy chain associates with β2-microglobulin.

The α1 and α2 domains form the peptide-binding groove.

The α3 domain provides a binding site for the CD8 coreceptor.

Peptide groove +

Heavy chain

β2-microglobulin

Stable MHC I

Slide 21 · CD8 T cells recognize class I complexes

A T-cell receptor contacts the peptide–MHC I complex.

CD8 binds to the nonpolymorphic α3 domain as a coreceptor.

Recognition can license cytotoxic action after appropriate activation.

Peptide–MHC I

TCR + CD8

Cytotoxic T-cell response

Slide 22 · Tumor recognition can use the class I pathway

Abnormal or mutated proteins in tumor cells can yield antigenic peptides.

These peptides may be displayed by MHC class I.

Cytotoxic T lymphocytes can recognize and kill tumor cells displaying such antigens.

Altered tumor protein

MHC I peptide

CD8 CTL target

Slide 23 · MHC class II expression is more restricted

MHC II is especially associated with professional antigen-presenting cells.

Dendritic cells present protein peptides to naive CD4 T lymphocytes.

Macrophages and B cells can display antigen to helper T cells during effector responses.

DC / macrophage / B cell

MHC II

CD4 T cell

Slide 24 · Class II antigen typically starts outside the cell

Extracellular microbes and proteins can be taken up by presenting cells.

They are delivered to endosomal or lysosomal compartments.

Proteolysis there prepares peptides for MHC II binding.

Extracellular protein

Internalization

Endosome / lysosome

Peptide

Slide 25 · Class II loading occurs in vesicles

Internalized proteins are broken down in intracellular vesicles.

The resulting peptides bind MHC II heterodimers.

Peptide–MHC II complexes then reach the cell surface.

Vesicular processing

Uptake

Extracellular protein

Endosome

Proteolysis and MHC II loading

Cell surface

Peptide–MHC II display

Slide 26 · MHC II consists of two polymorphic chains

Class II proteins contain an α chain and a β chain.

The α1 and β1 domains form the peptide-binding cleft.

The β2 domain supports binding of the CD4 coreceptor.

α / β chains

Peptide-binding

Groove

CD4 interaction

Slide 27 · CD4 T cells recognize class II complexes

The TCR recognizes the specific peptide–MHC II complex.

CD4 provides a coreceptor interaction with MHC II.

Activated helper cells can subsequently signal to macrophages or B cells.

Peptide–MHC II

TCR + CD4

Helper T-cell function

Slide 28 · MHC restriction explains T-cell recognition

CD8 T cells are class I restricted in conventional antigen recognition.

CD4 T cells are class II restricted in conventional antigen recognition.

A peptide alone is not equivalent to the peptide–MHC ligand seen by the TCR.

MHC I + peptide → CD8

MHC II + peptide → CD4

Compared with

Slide 29 · Endogenous and exogenous antigen pathways

Endogenous proteins enter the class I proteasome–ER route.

Internalized extracellular proteins enter the class II vesicular route.

This is a fundamental organizing principle, not a claim that every pathway lacks exceptions.

Cytosol/proteasome/ER

Endosome/lysosome/MHC II

Compared with

Slide 30 · B cells detect antigen without classical peptide–MHC restriction

The B-cell receptor is membrane-bound antibody.

It binds native antigens of several chemical types.

Recognized antigens may be proteins, polysaccharides, or lipids.

Native antigen

Membrane

Immunoglobulin

B-cell recognition

Slide 31 · T-cell and B-cell antigen recognition differ

Conventional T cells recognize processed peptides displayed by MHC.

B cells recognize native antigen with their membrane immunoglobulin receptor.

A B cell can later internalize a protein and present peptide–MHC II to helper T cells.

TCR: Peptide–MHC

BCR: Native antigen

Compared with

Slide 32 · A B cell can act as an antigen presenter

The BCR captures a protein antigen recognized by that B cell.

The protein is internalized, degraded, and displayed on MHC II.

A helper T cell recognizing the displayed peptide can deliver help.

BCR capture

MHC II presentation

Helper T cell

B-cell help

Slide 33 · Classical DCs and follicular DCs are different

Conventional DCs process antigen and present peptide–MHC to T cells.

Follicular dendritic cells trap antigen–antibody or complement complexes for B cells.

Their distinct mechanisms explain their localization in T-cell zones versus follicles.

Conventional DC → T cell

FDC → B cell

Compared with

Slide 34 · Follicular DCs retain antigen complexes

FDCs in germinal centers bear Fc receptors and complement-binding receptors.

They can capture immune complexes containing antigen.

This supports B-cell selection during antibody responses.

Immune complex

FDC retention

B-cell encounter

Slide 35 · Innate recognition precedes adaptive recognition

Innate cells use pattern-recognition receptors to sense microbial products.

This first response provides more than immediate defense.

It drives APC changes needed to efficiently activate naive lymphocytes.

Microbe

Pattern-recognition receptor

APC activation

Adaptive priming

Slide 36 · Dendritic cells carry sensors and presentation machinery

Dendritic cells express pattern-recognition receptors such as TLRs and lectins.

After microbial activation they increase MHC and activation-associated molecules.

Their biology unifies antigen capture, sensing, migration, and T-cell stimulation.

Capture + sense

Mature DC

Present and

Costimulate

Slide 37 · Microbial stimuli induce APC maturation

Microbes or adjuvants trigger innate responses.

APCs respond by expressing costimulatory molecules and producing cytokines.

Mature APCs can now provide more than peptide–MHC recognition to naive T cells.

Microbe / adjuvant

Activated APC

B7 + cytokines

T-cell priming

Slide 38 · B7 proteins are principal costimulators

CD80 and CD86 are the B7 proteins highlighted.

They are expressed by antigen-presenting cells after activation.

They engage the CD28 receptor on naive T cells.

APC CD80 / CD86

T-cell CD28

Slide 39 · CD28 receives APC costimulation

CD28 is expressed on naive T lymphocytes.

Its interaction with B7 occurs alongside antigen recognition.

CD28 signaling is distinct from the specificity provided by the TCR.

B7–CD28 contact

Costimulatory input

Slide 40 · Signal 1 determines antigen specificity

The TCR recognizes a particular peptide–MHC complex.

This provides the antigen-selective part of T-cell stimulation.

Signal 1 alone is not the complete activating context.

APC peptide–MHC

TCR

Antigen-selective signal 1

Slide 41 · Signal 2 provides activation context

Activated APCs express CD80/CD86 costimulators.

CD28 on the naive T cell recognizes these molecules.

This pathway couples T-cell activation to innate detection of microbial danger.

Microbial stimulus

APC B7

T-cell CD28

Signal 2

Slide 42 · Naive T cells integrate two cooperating signals

Signal 1 is antigen presented on an MHC molecule.

Signal 2 is supplied by APC costimulatory proteins.

Their cooperation supports antigen-specific lymphocyte activation.

APC

Naive T cell

Peptide–MHC → TCR

CD80 / CD86 → CD28

Signal 1

Signal 2

Both inputs act on the same responding T cell

Slide 43 · Why microbes activate immunity more reliably than harmless antigen

Microbial sensing drives APC costimulator expression.

A harmless protein without equivalent innate activation does not ordinarily produce the same activation context.

This is an important safeguard, although additional tolerance mechanisms also operate.

Microbe + costimulation

Harmless antigen alone

Compared with

Slide 44 · APC cytokines extend beyond costimulation

Activated APCs not only express B7 but also secrete cytokines.

Cytokines support the proliferation and differentiation of responding T cells.

Thus effective priming combines cell-contact and soluble inputs.

Antigen + B7

T-cell activation

Cytokine-guided expansion /

Differentiation

Slide 45 · Adjuvants mimic microbial activation cues

Protein-antigen immunization can include adjuvants.

Adjuvants stimulate innate immune responses that make antigen presentation more effective.

They are not simply additional target antigens for the same lymphocyte receptor.

Protein antigen + Adjuvant

Innate APC activation

Improved priming

Slide 46 · Damage cues can supply activation context

During tumor or transplant immune responses, signals may arise from injured cells.

Necrotic cells release damage-associated molecular patterns.

These signals can help induce costimulators even without microbial infection.

Necrotic cell

Damage-associated patterns

APC activation

Costimulation

Slide 47 · Tumor immunity uses abnormal antigens and danger context

Tumor cells may produce abnormal cytosolic proteins yielding class I peptides.

T-cell immunity can recognize tumor-associated peptide–MHC displays.

Local injury-related danger signals can contribute to immune activation context.

Tumor antigen

MHC I recognition + danger context

CTL response

Slide 48 · Transplants create both antigenic and innate stimuli

HLA diversity makes donor tissues immunologically distinct from recipients.

The source notes damage-associated signals in immune responses to transplants.

Antigen presentation and inflammatory context are both relevant to alloreactivity.

Donor HLA differences

+ tissue injury

Immune activation

Context

Slide 49 · Costimulation does not abolish self-tolerance

Self antigens may be displayed by APCs even during infection.

Increasing costimulator expression alone does not ordinarily cause a self-directed response.

Powerful immune control mechanisms restrain inappropriate recognition.

Self peptide display + APC activation

Additional tolerance safeguards

Slide 50 · Antigen recognition is necessary but not the whole story

Specific receptor engagement explains which lymphocyte is selected.

Costimulation and cytokines explain whether and how that lymphocyte responds.

Regulatory controls determine whether responses to self are permitted.

Specificity · Activation context

Control

Compared with

Slide 51 · Adaptive immunity follows an ordered response sequence

Recognition precedes lymphocyte proliferation and differentiation.

Effector and memory cells emerge after activation.

Antigen elimination is followed by contraction while memory cells persist.

Recognize

Expand

Differentiate

Eliminate

Contract / remember

Slide 52 · Activated T cells and B cells perform different tasks

Activated CD4 cells direct other cells through contact signals and cytokines.

Activated CD8 cells can differentiate into cytotoxic lymphocytes.

Activated B cells can develop into antibody-secreting plasma cells.

CD4 helper / CD8 CTL

/ B plasma cell

Immune response

Slide 53 · Lymph node versus spleen antigen capture

Lymph nodes concentrate antigens carried from tissues in lymph.

The spleen captures antigens circulating in the blood.

Both are secondary lymphoid organs supporting adaptive initiation.

Lymph-borne → node

Blood-borne → spleen

Compared with

Slide 54 · Mucosal lymphoid tissues survey epithelial entry

Lymphoid tissue lies beneath mucosal and cutaneous barriers.

These regions respond to microbes crossing epithelial surfaces.

Tonsils and Peyer patches are anatomically defined mucosal lymphoid tissues.

Epithelial challenge

Mucosal lymphoid

Response

Slide 55 · Primary and secondary lymphoid organs serve different roles

The thymus and bone marrow are primary organs of lymphocyte development.

Nodes, spleen, and mucosal/cutaneous tissues support antigen-driven responses.

Maturation and antigen encounter are distinct stages of lymphocyte biology.

Primary: Development

Secondary: Antigen-driven activation

Compared with

Slide 56 · T-cell zones optimize DC–T-cell encounters

DCs accumulate where naive T cells patrol, such as the lymph-node paracortex.

These contacts enable recognition of displayed peptide–MHC.

Cellular localization is as important as the binding specificity.

Paracortex

DC plus naive T cell

Priming

Slide 57 · Follicles optimize B-cell responses

B cells are enriched in cortical lymphoid follicles.

Follicular dendritic cells retain antigens for B-cell interaction.

Germinal centers appear when follicles contain activated responding B cells.

B-cell follicle

Antigen encounter

Germinal center response

Slide 58 · Antigen display must be distinguished from activation

A surface peptide–MHC complex can be displayed without ensuring full activation.

Naive T-cell activation also depends on appropriate costimulation.

Activated T cells later use cytokines and contacts to produce effector outcomes.

Display: Peptide–MHC

Activation: Signal 1 + signal 2

Compared with

Slide 59 · Case: Antigen enters through a skin wound

A microbial protein enters peripheral tissue beneath an epithelium.

Resident dendritic cells carry the antigen to draining lymph nodes.

Recognition by naive T cells is most likely where antigen and recirculating cells converge.

Applied mechanism

Skin entry

Migrating DC

Node paracortex

T-cell encounter

Slide 60 · Case: A virus produces proteins inside a cell

A viral protein is produced in the cytosol of a nucleated cell.

The class I pathway delivers cytosolic peptides to the surface.

CD8 T cells recognize the displayed peptide–MHC I complex.

Applied mechanism

Viral protein

MHC I

CD8 T cell

Slide 61 · Case: A vaccine protein is given with an adjuvant

An injected protein supplies antigen for adaptive recognition.

The adjuvant stimulates innate activation of APCs.

B7 expression and cytokine release help make priming effective.

Applied mechanism

Protein + adjuvant

Activated APC

T-cell priming

Slide 62 · Case: Infection occurs alongside self-antigen display

An infected tissue contains APCs that display both foreign and self peptides.

Microbial activation may upregulate costimulators on those APCs.

Costimulation alone does not override immune tolerance to self.

Applied mechanism

Infection

APC activation

Self-tolerance safeguards remain

Slide 63 · Integrated antigen-recognition model

Antigens are transported or concentrated in secondary lymphoid organs.

T cells inspect peptide–MHC with a requirement for appropriate activation context.

B cells recognize native antigen and may enlist T-cell help after processing protein antigens.

Capture

Present / recognize

Costimulate

Effector response

Slide 64 · Three questions to diagnose a presentation pathway

Where did the antigenic protein originate: Cytosol or extracellular space?

Which receptor sees it: Peptide–MHC-specific TCR or native-antigen-specific BCR?

Was the required APC context supplied to activate a naive T cell?

Antigen origin?

Receptor / MHC route?

Costimulation?

Slide 65 · Synthesis: Use the mechanism to interpret immunity

Antigen concentration solves the problem of rare antigen-specific lymphocytes.

MHC pathways determine which T-cell subset inspects a protein-derived peptide.

Antigen recognition, costimulation, and immune regulation jointly determine the response.

Slide 66 · Selected source material

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th edition (2026)

Chapter 6: Display and Recognition of Antigens.

Related sections: Major Histocompatibility Complex Molecules; Tissues of the Immune System.

Text content derived from the supplied chapter Markdown; textbook figure files not reproduced.