Immunology: MHC and Antigen Presenting Cells

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Questions and Answers

What is the primary role of MHC molecules in the immune system?

To bind and display peptides for T cell recognition. (correct)

To regulate the growth of T cells in the lymph nodes.

To produce antibodies for antigen neutralization.

To capture and destroy pathogens directly.

Which class of MHC molecules is found on all nucleated cells?

MHC III

MHC I (correct)

MHC IV

MHC II

Which of the following cells are primarily considered antigen presenting cells (APC)?

Red blood cells

Neutrophils

Killer T cells

B cells, macrophages, and dendritic cells (correct)

What is the significance of MHC polymorphism in the immune response?

It influences peptide binding and T cell recognition. Signup and view all the answers

Which T cell subtype is primarily activated by MHC II molecules?

CD4+ T lymphocytes Signup and view all the answers

What role do dendritic cells play in T cell activation?

They capture antigens and are the most effective APCs for naïve T cells. Signup and view all the answers

What regions of class I MHC molecules contain polymorphic residues responsible for peptide binding variations?

α1 and α2 domains Signup and view all the answers

Which class of MHC molecule accommodates longer peptides due to its open cleft structure?

Class II MHC molecules Signup and view all the answers

In which locations of MHC class II molecules are polymorphic residues found?

In the α1 and β1 segments Signup and view all the answers

What is the primary function of anchor residues of peptides in relation to MHC molecules?

To hold the peptide in the cleft of the MHC molecule Signup and view all the answers

What is the role of mechanisms of antigen processing in relation to MHC molecules?

To generate peptides with structural characteristics for MHC binding Signup and view all the answers

Which of the following best describes the closure of the cleft in class I MHC molecules?

It restricts binding to shorter peptides. Signup and view all the answers

What is the primary role of antigen-presenting cells (APCs) in T cell activation?

They present antigens and provide additional stimulatory signals. Signup and view all the answers

Which type of T cells are primarily activated by macrophages and B lymphocytes?

Previously activated CD4+ helper T cells Signup and view all the answers

What are co-stimulators in the context of T cell activation?

They are membrane-bound molecules of APCs that activate T cells. Signup and view all the answers

How do dendritic cells capture antigens from their environment?

Through pinocytosis and receptor-mediated endocytosis. Signup and view all the answers

What cytokine is important for activating dendritic cells in response to microbes?

Tumor necrosis factor (TNF) Signup and view all the answers

When activated, dendritic cells express a chemokine receptor that allows them to migrate to which part of the lymph nodes?

T cell zones Signup and view all the answers

What is the function of adjuvants in the immune response?

To enhance the expression of co-stimulators and cytokines. Signup and view all the answers

What occurs to dendritic cells upon activation by cytokines?

They start expressing the CCR7 receptor. Signup and view all the answers

What must happen for CD8+ T cells to recognize and kill virus-infected cells?

The infected cells must express MHC molecules belonging to the individual from which the CTLs were derived. Signup and view all the answers

What is the role of mature dendritic cells (DCs) in T cell activation?

They provide co-stimulatory signals and cytokines necessary for naive T lymphocyte activation. Signup and view all the answers

Which class I MHC genes are present in humans?

HLA-A, HLA-B, HLA-C Signup and view all the answers

What is true about MHC polymorphism?

Different individuals can present different peptides from the same protein antigen. Signup and view all the answers

What type of polypeptides compose each class II MHC molecule?

Heterodimers of α and β polypeptides Signup and view all the answers

What does the term 'MHC haplotype' refer to?

The set of MHC alleles present on a chromosome Signup and view all the answers

Where are MHC genes located in humans?

On the short arm of chromosome 6 Signup and view all the answers

How do T cells recognize antigens?

By recognizing peptide antigens bound to MHC molecules Signup and view all the answers

What is required for T cell antigen recognition to occur?

Binding to both a specific antigen and the corresponding MHC molecules. Signup and view all the answers

Study Notes

MHC Molecules

MHC molecules bind and display peptides for recognition by CD4+ and CD8+ T cells
MHC recognition is essential for T cell maturation, ensuring that mature T cells only recognize MHC molecules with bound antigens
MHC molecules are highly polymorphic, meaning they vary between individuals, influencing both peptide binding and T cell recognition

Antigen Presenting Cells (APCs)

APCs capture antigens from their site of entry or production and deliver them to lymphoid organs where naive T lymphocytes reside
APCs express class II MHC molecules and other molecules involved in stimulating T cells, capable of activating CD4+ T lymphocytes

Types of APCs

Dendritic cells are the most effective APCs for activating naive T cells and initiating T cell responses
Macrophages and B lymphocytes are more effective for previously activated CD4+ helper T cells rather than naive T cells

Functions of APCs

Antigens are the first signal for activating naive T cells, while co-stimulators act as second signals for activation
Co-stimulators are membrane-bound molecules on APCs that work alongside antigens to stimulate T cells
Adjuvants, derived from microbes, enhance the expression of co-stimulators and cytokines, also stimulating the antigen-presenting functions of APCs

Role of Dendritic Cells

Some antigens are transported in the lymph by APCs (primarily DCs) who capture the antigen and enter lymphatic vessels
Antigens that enter the bloodstream can be sampled by DCs in the spleen, or captured by circulating DCs and taken to the spleen
Resting tissue-resident DCs use receptors, like C-type lectins, to bind and endocytose microbes or microbial proteins, processing the ingested proteins into peptides capable of binding to MHC molecules
DCs can ingest antigens through pinocytosis, which does not involve specific recognition receptors, internalizing molecules in the vicinity of DCs
DCs are activated by cytokines, such as TNF, produced in response to microbes. Activated DCs (also called mature DCs) lose their adhesiveness for epithelia or tissues, and begin to express CCR7, a chemokine receptor specific for CCL19 and CCL21, chemokines produced in lymphatic vessels and T cell zones of lymph nodes

Dendritic Cells in Antigen Capture and Presentation

DCs are strategically located at common entry sites of microbes and foreign antigens (in epithelia) and in tissues colonized by microbes
DCs express receptors that enable them to capture and respond to microbes
DCs migrate from epithelia and tissues via lymphatics to T cell zones in lymph nodes where naive T lymphocytes circulate
Mature DCs express high levels of peptide-MHC complexes, co-stimulators, and cytokines, all necessary to activate naive T lymphocytes

MHC Discovery

If a mouse is infected with a virus, CD8+ T cells specific for the virus are activated and differentiate into CTLs. Analyzing the function of these CTLs in vitro, they recognize and kill virus-infected cells only if the infected cells express MHC molecules expressed in the animal from which the CTLs were removed
T cells must be specific for both the antigen AND MHC molecules. T cell antigen recognition is restricted by the MHC molecules a T cell sees.

MHC Genes

Polymorphic class I and class II MHC molecules are the ones responsible for displaying peptide antigens for recognition by CD8+ and CD4+ T cells, respectively.
The products of different MHC alleles bind and display different peptides, meaning different individuals may present different peptides even from the same protein antigen
For a given MHC gene, each individual expresses the alleles inherited from both parents, maximizing the number of MHC molecules available for binding peptides and presenting them to T cells

Human MHC Genes

In humans, the MHC is located on the short arm of chromosome 6, occupying a large segment of DNA (approximately 3500 kb)
There are three class I MHC genes called HLA-A, HLA-B, and HLA-C, which encode three types of class I MHC molecules with the same names
There are three class II HLA gene loci called HLA-DP, HLA-DQ, and HLA-DR. Each class II MHC molecule is composed of a heterodimer of α and β polypeptides.
The set of MHC alleles present on each chromosome is called an MHC haplotype
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  ### Polymorphic Residues of MHC Molecules
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The polymorphic residues of class I molecules are confined to the α1 and α2 domains, contributing to variations among different class I alleles in peptide binding and T cell recognition.
The polymorphic residues of class II molecules are located in the α1 and β1 segments, in and around the peptide-binding cleft, similar to class I MHC molecules.
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  ### Peptide Binding to MHC Molecules
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The class I molecule shown is HLA-A2, and the class II molecule is HLA-DR1. The cleft of the class I molecule is closed, while the cleft of the class II molecule is open. As a result, class II molecules accommodate longer peptides than class I molecules.
Side view of a peptide bound to a class II MHC molecule shows how anchor residues of the peptide hold it in the pockets of the MHC molecule cleft.
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  ### Processing of Protein Antigens
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Antigen processing mechanisms are designed to generate peptides with structural characteristics necessary for associating with MHC molecules, placing these peptides in the same cellular location as newly synthesized MHC proteins with available peptide-binding clefts.
Cytosolic proteins are degraded by proteasomes to yield peptides displayed on class I MHC molecules, while proteins ingested from the extracellular environment and sequestered in vesicles are degraded in lysosomes (or late endosomes) to generate peptides presented on class II MHC molecules

Class I MHC Pathway for Processing and Presentation of Cytosolic Proteins

Microbial proteins in the cytosol that undergo proteasomal degradation are derived from microbes (usually viruses) that replicate and survive in the cytosol, extracellular bacteria that inject proteins into the cytosol, and various extracellular organisms that are phagocytosed, with their proteins transported from vesicles into the cytosol
Degradation of proteins in proteasomes generates peptides capable of binding to class I MHC molecules
Peptides generated by proteasomes in the cytosol are translocated by a specialized transporter (TAP) into the ER, where newly synthesized class I MHC molecules are available to bind the peptides.
Class I MHC molecules with bound peptides are structurally stable and are expressed on the cell surface.

Class II MHC Pathway for Presentation of Proteins Degraded in Lysosomes

Most class II MHC-associated peptides are derived from protein antigens digested in endosomes and lysosomes in APCs.
Internalized proteins are degraded enzymatically in late endosomes and lysosomes to generate peptides capable of binding to the peptide-binding clefts of class II MHC molecules.

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Description

This quiz covers the critical roles of MHC molecules and antigen presenting cells (APCs) in the immune response. It delves into how MHC molecules bind peptides for T cell recognition and the functions of various APC types in activating naive T lymphocytes. Test your knowledge on the intricacies of T cell activation and the significance of APCs.