Immunology Lesson: Antigen Processing, MHC Types & T Cells

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Lesson Overview

When Samantha blanked out on how T cells identify infected cells during her biology exam, she realized memorizing terms wasn't enough. Understanding immunology means tracing how antigens are processed and matched with the right T cells. This lesson breaks it all down simply so you can learn it once and learn it well.

What Is Immunology and Why Is It Important?

This section introduces immunology as the science of immune protection, surveillance, and regulation in living organisms.

Immunology is the scientific discipline that studies how the immune system defends the body against harmful pathogens such as bacteria, viruses, fungi, and parasites. Immunology focuses on identifying how immune cells recognize foreign substances, eliminate them, and develop memory for future protection. Immunological knowledge is vital in understanding:

  • Disease mechanisms (e.g., infections, autoimmunity)
  • Vaccine development
  • Transplantation compatibility
  • Allergies and hypersensitivities
  • Immunodeficiencies (e.g., HIV/AIDS)

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How Do T Cells Recognize and Respond to Antigens?

This section explores the role of T lymphocytes and how their receptors interact with MHC-peptide complexes.

T cells are specialized white blood cells that mediate adaptive immune responses. T cells detect antigens through T-cell receptors (TCRs), but only when antigens are processed and presented on MHC (Major Histocompatibility Complex) molecules.

  • CD4+ T cells recognize peptides presented by MHC Class II molecules on antigen-presenting cells.
  • CD8+ T cells recognize peptides on MHC Class I molecules present on all nucleated cells.

This MHC-restricted recognition ensures that:

  • CD4+ T cells assist extracellular immune responses.
  • CD8+ T cells eliminate infected or cancerous host cells.

Where Are MHC Molecules Located and What Do They Do?

This section identifies MHC distribution and correlates it with their respective immune functions.

MHC molecules are glycoproteins encoded by the HLA (human leukocyte antigen) gene complex. Their function and location include:

MHC TypeExpressed OnPresents Peptides FromRecognized By
Class IAll nucleated cellsCytosolic/intracellular originCD8+ T lymphocytes
Class IIDendritic cells, macrophages, B cellsEndocytic/extracellular originCD4+ T lymphocytes

How Does the Immune System Process Intracellular Antigens?

This section explains the cytosolic pathway for antigen processing and Class I MHC presentation.

Intracellular pathogens such as viruses generate proteins in the cytoplasm. These undergo:

  • Proteasomal degradation into peptides (8–11 amino acids)
  • Transport into the ER by TAP
  • Binding to MHC Class I molecules
  • Trafficking through the Golgi to the cell surface

This pathway enables cytotoxic CD8+ T cells to recognize and kill infected cells.

How Are Extracellular Antigens Processed for Immune Activation?

This section describes the endocytic pathway and MHC Class II-dependent presentation.

Antigens from bacteria and other extracellular microbes undergo the following process:

  • Uptake into endosomes via phagocytosis or receptor-mediated endocytosis
  • Proteolysis in lysosomes into antigenic peptides
  • Synthesis of MHC Class II and invariant chain in the ER
  • Transport of MHC II to the lysosome
  • Degradation of the invariant chain and peptide binding
  • Surface expression of the MHC-peptide complex for CD4+ T cell recognition

What Is the Role of the Invariant Chain in MHC Class II Processing?

This section details the protective and regulatory function of the invariant chain in antigen presentation.

The invariant chain (Ii) has key functions:

  • Binds MHC Class II in the ER to stabilize the molecule
  • Blocks premature peptide binding
  • Guides MHC Class II to the late endosome/lysosome
  • Is enzymatically degraded, leaving CLIP (Class II-associated invariant chain peptide)
  • Allows antigen peptides to replace CLIP with the help of HLA-DM

How Does the TAP Transporter Facilitate Class I MHC Function?

This section outlines TAP's role in delivering peptides from the cytoplasm into the ER for Class I presentation.

TAP (Transporter associated with Antigen Presentation):

  • Is a heterodimer of TAP1 and TAP2 proteins
  • Resides in the ER membrane
  • Uses ATP to move peptides (8–16 residues) into the ER
  • Provides peptides for loading onto MHC Class I
  • Is essential for efficient CD8+ T cell activation

How Do Genetic Defects in TAP Affect Immune Function?

This section describes the clinical consequences of TAP mutations and their immunological impact.

Defective TAP results in:

  • Low MHC Class I expression
  • Impaired peptide presentation
  • Weak CD8+ T cell activation
  • Increased susceptibility to recurrent infections (especially respiratory)

Clinically, this condition may resemble chronic respiratory infections with poor viral clearance.

How Do Viruses Escape Detection by the Immune System?

This section explores how viral proteins manipulate MHC expression and antigen processing.

Viruses use sophisticated evasion strategies:

  • Adenoviruses suppress MHC I transcription → fewer MHC I molecules
  • HSV blocks TAP transporter → reduced peptide availability

Consequences of immune evasion include:

  • Reduced antigen presentation
  • Impaired T cell surveillance
  • Persistent or latent infections
VirusImmune Evasion MechanismEffect on Immune Response
AdenovirusInhibits MHC I gene expressionDecreases CD8+ T cell recognition
Herpes (HSV)Blocks TAP transporterPrevents peptide loading

How Do the Cytosolic and Endocytic Pathways Compare?

This section contrasts the two major antigen processing routes in immune defense.

FeatureCytosolic Pathway (Class I)Endocytic Pathway (Class II)
Pathogen TypeIntracellular (e.g., viruses)Extracellular (e.g., bacteria)
MHC Class UsedClass IClass II
T Cell ActivatedCD8+ cytotoxic T cellsCD4+ helper T cells
Processing CompartmentCytosol, EREndosome, lysosome
Transporter RequiredYes (TAP)No
Invariant Chain UsedNoYes
Peptide Length8–11 amino acids13–25 amino acids

Why Does Antigen Presentation Matter in Immunology?

This section explains the physiological significance of peptide-MHC display in immune regulation.

Antigen presentation serves several key roles:

  • Activates T cells to mount an adaptive immune response
  • Distinguishes infected or abnormal cells from healthy ones
  • Enables immune memory and vaccine effectiveness
  • Coordinates communication between innate and adaptive arms

Disruptions in antigen processing can result in:

  • Immunodeficiency
  • Chronic infection
  • Autoimmunity

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