MHC and T Cell Activation

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Questions and Answers

What type of T cells interact with MHC class I molecules?

Memory T cells

Regulatory T cells

CD8+ T cells (correct)

CD4+ T cells

Which part of the CD4 molecule interacts with MHC class II specifically?

D1 domain (correct)

D2 domain

D3 domain

D4 domain

What is the role of CD4 in T cell activation?

It enhances signal transduction from the TCR. (correct)

It forms a dimer with CD3.

It causes destruction of self-reactive T cells.

It presents antigens to B cells.

Which molecule is not involved in the CD4 signaling cascade?

IgM Signup and view all the answers

What happens during negative selection of T cells in the thymus?

T cells expressing high affinity for self-antigens are eliminated. Signup and view all the answers

Which component is part of MHC class I?

Beta-2 microglobulin Signup and view all the answers

What is the primary consequence of TCR and CD4 co-receptor binding to an MHC molecule?

Phosphorylation of ITAMs for signal amplification Signup and view all the answers

What structural feature distinguishes CD4 from CD8?

CD4 has four immunoglobulin domains. Signup and view all the answers

Which transcription factors are activated by the signaling cascade involving CD4?

AP-1 and NF-kB Signup and view all the answers

Which T cell receptor is CD8 commonly found with?

TCR that recognizes MHC class I Signup and view all the answers

What are the primary components of the common form of CD8?

CD8-α and CD8-β Signup and view all the answers

Which part of the Class I MHC molecule interacts with CD8-α?

α3 domain Signup and view all the answers

In CD8+ T cells, what is the primary role of the CD8 co-receptor?

Aid cytotoxic T cell antigen interactions Signup and view all the answers

What initiates the phosphorylation cascade in T cell activation?

T cell receptor binding specific antigen Signup and view all the answers

Which ligand is associated with CD28 for T cell activation?

B7-1 Signup and view all the answers

What is the effect of upregulating CTLA4 in T cells?

Inhibits T cell responses Signup and view all the answers

The two-signal hypothesis for T cell activation requires interaction with which molecules?

Antigen and CD28 ligand Signup and view all the answers

What happens to CD28 expression when CTLA4 is upregulated?

Decreased expression through endocytosis Signup and view all the answers

Which transcription factors are activated following Lck phosphorylation in T cells?

NFAT and NF-κB Signup and view all the answers

What do the cytoplasmic tails of CD8 interact with?

Lck Signup and view all the answers

What is the primary function of MHC proteins?

To present peptide fragments on the cell surface Signup and view all the answers

Which type of T cell is primarily associated with MHC I molecules?

CD8+ T cells Signup and view all the answers

What is the role of CD4+ T cells in relation to MHC II molecules?

They recognize antigens presented by MHC II molecules and provide help to B cells. Signup and view all the answers

How do T cells recognize antigens?

By using T cell receptors that recognize peptide-MHC complexes Signup and view all the answers

Which of the following statements about the endogenous pathway of antigen presentation is correct?

It is used by CD8+ T cells to detect intracellular pathogens. Signup and view all the answers

What characteristic differentiates MHC I from MHC II molecules?

MHC I is present on all nucleated cells, while MHC II is only found on antigen-presenting cells. Signup and view all the answers

What is one way T cells are prevented from being 'distracted' by free antigens?

By requiring recognition through MHC molecules for activation Signup and view all the answers

Which motif is recognized by Src kinases in T cell activation?

Immunoreceptor tyrosine-based activation motif (ITAM) Signup and view all the answers

What is a consequence of antigen presentation systems evolving?

T cells are directed to interact with specific cells harboring pathologic threats. Signup and view all the answers

What type of antigens are typically presented by MHC II molecules?

Exogenous antigens that have been ingested Signup and view all the answers

Study Notes

MHC and Antigen Presentation & T Cell Activation

MHC proteins bind to peptide fragments and display them on the cell surface, acting like a barcode.
T cells use MHC proteins to identify abnormal proteins on cells, potentially due to viral/bacterial invasion, cancer, or foreign cells.
MHC, a major histocompatibility complex, is a tightly linked cluster of genes present in vertebrates.
These genes regulate intercellular recognition and self/non-self discrimination.
MHC is located on chromosome 6 in humans and chromosome 17 in mice.

MHC Classes

MHC genes are organized into three classes.
Class I MHC genes: Glycoproteins expressed on all nucleated cells. Their main function is to present peptide antigens to cytotoxic T cells (Tc cells).
Class II MHC genes: Glycoproteins expressed on antigen-presenting cells (APCs) like macrophages, B cells, and dendritic cells. Their main function is to present processed antigen peptides to helper T cells (TH cells).
Class III MHC genes: Not membrane proteins. They aren't directly involved in antigen presentation but play roles in the immune response, including complement components and heat shock proteins.

MHC Class I Molecules

Molecular weight: 45 kD.
Found on almost all nucleated cells (except red blood cells).
Bind to portions of antigens (peptide fragments).
Presents the fragments on the cell surface.
Cytotoxic T cells recognize and initiate specific immune defenses against cells with these displayed antigens.

MHC Class I Protein Structure

Membrane-spanning molecule, approximately 350 amino acids long.
Transmembrane and cytoplasmic portions comprise 75 amino acids.
Remaining 270 amino acids are divided into three globular domains (α1, α2, and α3).
A second portion called β2-microglobulin is associated with the a3 domain, crucial for MHC stability.
β2-microglobulin is a highly conserved protein encoded on different chromosomes.
α1 and α2 domains form an 8-antiparallel β-strand structure connected by two long α-helices creating a peptide-binding cleft.
The cleft can contain small 8-10 amino acid peptides and present these peptide fragments to T cells.

MHC Class II Molecules

Composed of two polypeptide chains (alpha and beta).
About 230 and 240 amino acids long, respectively, and glycosylated, giving molecular masses of approximately 33 kDa and 28 kDa.
The polypeptide chains fold into two separate domains (a1 and a2 for alpha, and β1 and β2 for beta).
A region between the α1 and β2 domains is similar to Class I MHC, acting as a peptide-binding cleft for 10–15 amino acid peptides.

MHC II Structure Overview

MHC II molecules are composed of a polymorphic α-chain and a non-polymorphic β-chain joined non-covalently.
Both chains are glycosylated.
The cleft, formed by portions of the α and β polypeptide chains, is a site where antigenic peptides are presented on the cell surface to T cells..

Antigen Processing and Presentation

Foreign proteins are degraded into small antigenic peptides.
Peptides combine with MHC I or II molecules.
This process is called antigen processing and presentation. The route the antigen takes into the cell determines if it is processed and presented with MHC I or MHC II.

Endogenous Pathway

Endogenous antigens originate within the cell (e.g., viral proteins, proteins from cancerous cells).
These proteins are degraded into peptides in the endoplasmic reticulum, and the peptides bind to MHC I molecules.
MHC I-peptide complexes are transported to the cell surface, where they are recognized by cytotoxic T cells (CD8+).

Exogenous Pathway

Exogenous antigens originate outside the cell (e.g., ingested bacteria).
These antigens are engulfed by the cell via endocytosis or phagocytosis.
Inside the cell, the antigens are degraded into peptides within endocytic vesicles.
Peptides bind to MHC II molecules within the endocytic vesicles.
MHC II-peptide complexes are transported to the cell surface, where they are recognized by helper T cells (CD4+).

T-Cells

Develop in the thymus.
Involved in cell-mediated immunity.
Feature: T cell receptor (TCR).
Types include helper, cytotoxic, memory, regulatory, and γδ T cells.
T cells eliminate pathogens in infected cells and assist B cells in antibody production.
T cells identify and eliminate cells harboring pathogens.

T Cell Receptor (TCR)

A protein complex found on T cells.
Recognizes peptides bound to MHC molecules (not freely circulating peptides).
TCR is part of the immunoglobulin superfamily.
The TCR is a heterodimer (either αβ or γδ) – two disulfide-linked polypeptide chains normally consisting of highly variable α and β chains expressed as part of complex with invariant CD3 chain molecules.
TCR diversity arises from a combinatorial approach of diverse chains.

TCR Diversity

TCRs are highly variable in individuals.
Antibody diversity is similar..
TCR diversity is due to small changes in the charge and shape; random aspects of TCR structure contribute..
TCR diversity and generation mechanisms are analogous to immunoglobulin genes.

The Challenge T Cells Face

Require a large number of T cell clones (~10¹³).
Peptides are ~10 amino acids long.
Millions of possible peptides with various amino acid combinations.
Multiple germline segments are combined for TCR diversity. Somatic recombination and selection mechanisms form the basis for massive TCR diversity and avoid self-recognition.

CD4 Co-Receptor

CD4 is a co-receptor for TCR in helper T cells.
It binds to MHC class II molecules.
Its intracellular domain binds to Lck tyrosine kinase.
CD4 mediates TCR signaling and intracellular cascade events.

CD8 Co-Receptor

CD8 is a co-receptor for TCR in cytotoxic T cells; it's expressed as a dimer (alpha and beta chains).
It binds to class I MHC molecules.
CD8 ensures tight binding and delivers downstream signals through Lck to TCR

B7-CD28 Co-stimulation

Crucial for T cell activation.
Requires both antigen recognition and co-stimulation (e.g., B7-1 and B7-2 interacting with CD28).
Prevents activation by antigens on normal cells.
Suppresses T cell responses when CTLA4 is activated.

Lymphocytes (T cells and B cells)

Immature lymphocytes from bone marrow are fundamentally similar.
T cell maturation takes place in the thymus.
B cell maturation occurs in the bone marrow.

T-Cell Types

Helper T cells (CD4+) secrete cytokines to activate B and other immune cells.
Cytotoxic T cells (CD8+) directly eliminate infected cells.
Regulatory T cells (Tregs) modulate immune responses.

Key Steps in T-cell Activation

APC's have to process and present peptides to T cells (either exogenously or endogenously produced).
T cell binding to APC requires secondary signal of costimulatory molecules.
Accessory adhesion molecules help stabilize the binding.
Cytokine signals from cell surfaces are relayed to the cell nucleus for division.

MHC Class III

Contains components crucial for the formation of complement convertase (e.g., C2, C4, and factor B).
Includes heat shock proteins and tumor necrosis factors.

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Description

Explore the critical role of MHC proteins in antigen presentation and T cell activation. This quiz covers the organization of MHC classes and their function in immune response. Test your understanding of how these proteins help T cells identify abnormal proteins in the body.