Lecture 3: Antigen Recognition by T lymphocytes

Questions to Consider

How do B cells and T cells see antigen?

How does a T cells distinguish between whether a foreign antigen is being presented to recruit help or because the cell is infected?

Why do some T cells kill and others provide help?

Phagocytosis by Macrophages

Antigen Presenting Cells

Activation of Macrophages PermitsElimination of Mycobacterium Infection

Changes Exhibited by an Activated Macrophage

Development of a Secondary Amplified Response

T-cell Activation of Macrophages

Transfer of Which Cells Will Protect This Mouse From TB?

Activated monocytes

T cells

B cells

T-cell Activation of Macrophages Permits Killing of Phagocytosed Pathogens

How does the T cell know that the macrophage is infected with TB?

B Cells and T Cells Use Different Antigen-specific Receptors

T Cell Receptor Gene

Genetic Rearrangement Generates T Cell Receptor Diversity

Development of a Secondary Amplified Response

T Cells and B Cells Recognize Antigen Differently

Secondary Immune Response

Primary Immunization

Secondary Ag Challenge B Cell Response T Cell Response

Native Protein Native Protein + + Denatured

Protein Native Protein - +

Native Protein Denatured Protein - +

Denatured Protein

Denatured Protein + +

The T Cell Receptor Only Recognizes Antigen in the Presence of Antigen Presenting Cells

Abbas- Cellular and Molecular Immunology

Antigen Must Be Processed to Peptides to be Recognized by the T Cell Receptor

Abbas- Cellular and Molecular Immunology

Antibody and T Cell Receptors Recognize Different Antigenic Contexts

B Cells use the Immunoglobulin Molecule to recognize 3D structures of the native molecules.

T Cells use theT cell receptor to recognize primary structures.

While the Majority of MHC-expressed Peptides are Self Self-reactive T Cells Are Not Present in the Periphery

Abbas- Cellular and Molecular Immunology

Two Different Types of MHC Molecules Are Capable of Presenting Peptides to T Cells

Divergent Cellular Expression of Class I and Class II MHC Molecules

Peripheral T Cells Express Either CD4 or CD8 Molecules

TCR Interaction With APCs Is Limited by CD4 or CD8 to Either MHC Class I or II, Respectively

Functional Implication of CD4 or CD8 Restricted Recognition of Class I or Class II MHC Molecules

Abbas- Cellular and Molecular Immunology

MHC Class I Molecules Only Present Peptides Derived From Endogenous Proteins

Cells Expressing Foreign Peptides Recognizedby Cytotoxic CD8+ T Cells Are Killed

Antigen Presenting Cells

MHC Class II Molecules Present Only Peptides Derived From Exogenous Proteins

Mon

ocyt

esB

Cel

ls

CD4+ T Cells Stimulate Cells Expressing Foreign Peptides That They Recognize

B Cells Present Peptides Derived FromProteins Recognized by Surface Antibody

Correlation of Pathogen Location, MHC Presentation and T Cell Effector Function

NATURE |VOL 391 | 22 JANUARY 1998

Natural Killer (NK) Cells Prevent Evasion of CTL Immunity by Downregulation of MHC Class I MHC Molecules

Killer inhibitory receptors- KIR interact with MHC and prevent the NK cells from killing target cells

HIV Can Evade This Immune Response Too

Questions to Consider

How do B cells and T cells see antigen?

How does a T cells distinguish between whether a foreign antigen is being presented to recruit help or because the cell is infected?

Why do some T cells kill and others provide help?