Antigen Presentation to Lymphocytes

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Questions and Answers

Which HLA allele is very strongly associated with Ankylosing spondylitis?

DR4

DQ2

DQ8

B27 (correct)

Which disease is linked to the HLA allele DQ2?

Celiac disease (correct)

Rheumatoid arthritis

Type 1 diabetes (correct)

Ankylosing spondylitis

What is the role of the invariant chain (Ii) in the Class II MHC pathway?

It degrades extracellular proteins.

It pumps peptides into the ER.

It stabilizes the MHC-I molecule.

It binds to Class II MHC and directs it to the lysosome. (correct)

Which HLA allele has a strong association with Type 1 diabetes?

DQ8 Signup and view all the answers

Which statement accurately describes the inheritance of HLA class II genes?

Individuals inherit two HLA class II genes for both α and β chains from each parent. Signup and view all the answers

In the ubiquitin-proteasome pathway, what is the primary role of ubiquitin?

To tag cytosolic proteins for degradation. Signup and view all the answers

What is the primary function of MHC class I molecules?

To present intracellular antigens to cytotoxic T lymphocytes. Signup and view all the answers

How do MHC molecules react to self antigens?

T cells specific for self antigens are either killed or inactivated. Signup and view all the answers

What is a function of the transporter associated with antigen processing (TAP)?

It transports peptides into the ER. Signup and view all the answers

Which of the following diseases is characterized by joint inflammation and associated with HLA allele DR4?

Rheumatoid arthritis Signup and view all the answers

What characterizes the antigen presentation capability of MHC molecules?

MHC molecules are capable of presenting non-peptide antigens such as small molecules and metal ions. Signup and view all the answers

What is the main function of CD8+ T cells as described in the immune response?

To recognize and destroy infected target cells. Signup and view all the answers

Which of the following best explains the clinical significance of MHC molecules in organ transplants?

MHC classes I and II can induce graft rejection due to immune recognition. Signup and view all the answers

What is the primary function of MHC molecules in the immune response?

Display peptide antigens for recognition by T lymphocytes Signup and view all the answers

Which of the following describes the maturation process of dendritic cells?

Expression of chemokine receptor CCR7 for migration Signup and view all the answers

What role does the Transporter associated with Antigen Processing (TAP) play in relation to MHC molecules?

It facilitates the translocation of peptides into the ER for MHC binding Signup and view all the answers

Which aspect of MHC class I molecules allows them to interact with CD8 T cells?

The invariant α3 domain of the α chain Signup and view all the answers

How many alleles are present in the human HLA system?

Thousands, with more than 4,600 HLA-A alleles Signup and view all the answers

What is an important change in dendritic cells following their recognition of a pathogen?

Loss of adhesiveness to tissues Signup and view all the answers

What is the structural composition of MHC class II molecules?

Two transmembrane chains: α2 and β2 Signup and view all the answers

Why are the MHC genes considered polymorphic?

They exhibit a large number of different alleles Signup and view all the answers

What is the primary function of CD4+ T helper cells in relation to B cells?

To stimulate B cells to divide and differentiate into plasma cells Signup and view all the answers

What is the process by which dendritic cells can present antigens from infected cells?

Cross-presentation of antigens via MHC class I molecules Signup and view all the answers

Which of the following statements about immuno-dominant peptides is true?

They represent peptides that can be presented for T cell recognition Signup and view all the answers

What is a key difference between follicular dendritic cells (FDCs) and classical dendritic cells?

FDCs display intact antigens to activated B cells without the role of MHC Signup and view all the answers

Which statement correctly describes the role of antigen presenting cells (APCs)?

APCs provide additional signals for T cell activation through costimulation Signup and view all the answers

What activates CD8+ T lymphocytes after antigen presentation?

Presence of costimulatory signals from dendritic cells Signup and view all the answers

Why are CD8+ T lymphocytes important in the immune response?

They directly kill infected or cancerous cells. Signup and view all the answers

What is NOT a characteristic of dendritic cells?

They serve to directly stimulate B cells without any additional signals. Signup and view all the answers

Study Notes

Antigen Capture and Presentation to Lymphocytes

Lymphocytes recognize peptides bound to MHC molecules on antigen-presenting cells (APCs)
Key study points include: how rare naive lymphocytes find microbes specifically and how different types of T cells recognize microbes in different cellular compartments
APC's (e.g., dendritic cells) capture antigens and present them on MHC molecules
MHC molecules display peptide antigens to T cells, triggering an immune response

Antigens Recognized by T-Lymphocytes

The majority of T lymphocytes recognize peptide antigens bound to MHC molecules of APCs
T cells contact a residue of peptide
Polymorphic residue of MHC
Anchor residue of peptide
"Pocket" of MHC
Peptide

Capture and Display of Microbial Antigens

Microbes are captured by lymphatic vessels and connective tissue and travel to lymph nodes
Antigens enter the blood stream via venules
Antigens are captured by antigen-presenting cells in the spleen
Antigen presentation occurs in the lymph nodes, and spleen
Different types of dendritic cells (classical and plasmacytoid) play critical roles in capturing and presenting antigens
Selected surface markers (human)
CD11c, BDCA2 (CD303), BDCA1 (CD1c), Dectin
TLRs 4, 5, 8, and TLRs 7, 9
Major cytokines expressed
TNF, IL-6, IL-12, IL-23 , Type I interferons

Antigen Uptake, Maturation, and Migration of Dendritic Cells

Dendritic cells (DCs) express Pattern Recognition Receptors (PRRs), including Toll-like receptors (TLRs) and C-type lectin receptors (CLRs)
DC maturation occurs upon pathogen recognition or cytokine signaling (like TNF, IL-1)
Maturation markers include CD40, CD80, and CD86
Loss of adhesiveness
Expression of chemokine receptor (CCR7)
Migration to lymphoid organs to present antigens
Increase in MHC class II expression

Major Histocompatibility Complex (MHC)

MHC (HLA) is a genetic locus that determines tissue graft acceptance or rejection
Codes for membrane proteins on antigen-presenting cells
Code for the transporter associated peptide (TAP)
MHC III contain genes for complement C2, C4, factor B and cytokines
HLA system is the most polymorphic gene system in humans
Thousands of alleles
Each person has two HLA alleles of each type (haplotype)

Structure of MHC Molecules

Class I MHC:
Consists of a chain non-covalently associated with β2-microglobulin
a domain consisting of two walls and an amino acid peptide-binding cleft
Peptide-binding cleft floor amino acids bind peptides
The wall makes contact with TCR
MHC-I polymorphism occurs mostly in the alpha chain amino acid residue
α3 domain is invariant and contains a site that binds the CD8 coreceptor
Class II MHC:
Consists of two transmembrane chains (α2 and β2)
Amino-terminal regions of both chains (α1 and β1 domains) contain polymorphic residues and form a cleft
β2 domains contain the binding site for the CD4 T cell co-receptor

Properties of Major Histocompatibility Complex (MHC) Molecules and Genes

Located on the short arm of chromosome 6
Each person inherits one HLA class I gene (A, B, C) from each parent
Each person inherits two HLA class II genes (DP, DQ) encoding for the alpha chain and beta chain from each parent
Each HLA allele is given by a numeric designation (e.g., HLA-A2, B5, DR3, etc.)

Antigen Capture and Presentation to Lymphocytes (continued)

Reactions of MHC molecules:
May be involved in reactions of T cells to nonpeptide antigens (e.g., small molecules or metal ions)
Class I MHC proteins (A, B, and C) present intracellular antigens (e.g., from viruses or tumors) to cytotoxic T lymphocytes
MHC class II proteins (DR, DQ, and DP) present extracellular antigens to T helper cells
A single T cell only needs to recognize a peptide displayed on 0.1% to 1% of the approximately 10⁵ MHC molecules on the surface of an APC
MHC molecules cannot discriminate between self and foreign antigens
T cells specific for self-antigens are killed or inactivated

Clinical Significance of MHC

Important in tissue transplant procedures
MHC classes I and II can induce graft rejection
Certain HLA types appear to play a role in autoimmune diseases

Association of HLA Alleles and Disease

Various diseases, such as ankylosing spondylitis, celiac disease, rheumatoid arthritis, and type 1 diabetes, have associations with specific HLA alleles.

Class I MHC Pathway of Processing of Cytosolic Antigens

Cytosolic proteins (unfolded and tagged with ubiquitin) are degraded into peptides by the proteasome
Transporter associated with antigen processing (TAP) transports peptides into the endoplasmic reticulum (ER)
TAP pumps peptides into the ER
Chaperone (like Tapasin) stabilizes newly synthesized class I MHC molecules in the ER by attachment to TAP

Tc Recognize and Destroy Target Cells

CD8+ T cells bind to the antigen-MHC class I complex on the target cell surface
T cells release enzymes (e.g., perforins, granzymes) that destroy the target cell

Class II Major Histocompatibility Complex Pathway of Processing of Internalized Vesicular Antigens

Extracellular microbes or proteins are ingested by phagocytosis
Proteins are broken down in acidic vesicles (like endosomes or phagosomes)
Invariant chain (Ii) binds to class II MHC molecules in the ER, directing them to endosomes
Ii is degraded, releasing CLIP (invariant chain peptide) from the cleft
HLA-DM exchanges CLIP with other peptides to load MHC class II molecules

Th Assist Antibody Production

CD4+ T helper cells stimulate B cells to differentiate into antibody-producing plasma cells (secreting antibodies)

Class I MHC-Restricted Cross-Presentation

A subset of classical dendritic cells can ingest infected host cells, dead tumor cells, microbes, and microbial antigens
Transport antigens to the cytosol
Process antigens through the proteasome
Display antigenic peptides bound to class I MHC molecules for CD8+ T cell recognition
Differentiated CD8⁺ cells kill infected host cells or tumor cells without dendritic cell assistance.
Occurs when viruses infect cells other than dendritic cells or tumors arise from different cell types

Role of MHC-Associated Antigen Presentation

Immuno-dominant peptides bind the MHC molecules in a specific way presented to T-cells
Class I MHC pathway presents antigens to cytotoxic T lymphocytes
Class II MHC pathway presents antigens to helper T cells

Functions of Antigen Presenting Cells

Display peptides for recognition by T-cells
Express additional signals (like B7-CD80, CD86 binding to CD28) for T-cell activation

Antigen Recognition by B-Cells and Other Lymphocytes (Follicular Dendritic Cells)

Follicular dendritic cells (FDCs) are found in B-cell-rich lymphoid follicles (lymph nodes and spleen)
They display intact native antigens bound by antibodies (or complement as C3b, C3d) to activate B cells, and induce affinity antibody maturation
FDCs aren't derived from bone marrow
Unlike other dendritic cells, FDCs don't process or present antigens to T cells

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Description

This quiz focuses on the mechanisms of antigen capture and presentation to lymphocytes, essential for immune response. Key concepts cover how MHC molecules interact with peptides, allowing T cells to recognize and respond to microbial antigens. Understand the roles of antigen-presenting cells and the pathways that lead microbes to lymph nodes and the immune system.