T-cell guides

What are the 3 signals required for T-cell activation?

TCR + peptide-MHC + CD4/CD8 coreceptor

Costimulation, including CD28

Cytokines

What is Signal 1 for T-cell activation?

TCR recognition of peptide-MHC, supported by the CD4 or CD8 coreceptor.

What is Signal 2 for T-cell activation?

Costimulation, including CD28.

What is Signal 3 for T-cell activation?

Cytokines.

What does MHC class II present antigen to?

CD4+ T cells (helper T cells).

What does MHC class I present antigen to?

CD8+ T cells (cytotoxic T cells).

What kinase associates with CD4 and CD8?

Lck, which helps initiate signaling.

What molecules strengthen the interaction between T cells and APCs?

Adhesion molecules. The guide lists molecules including LFA-1 and ICAM-1 in this context.

What molecules interact with CD28 to provide costimulation?

CD80/CD86 on the antigen-presenting cell.

What happens after successful T-cell activation?

Survival → proliferation → differentiation.

What is the overall function of costimulatory signals?

Promote optimal T-cell activation.

What is the overall function of coinhibitory signals?

Prevent/inhibit T-cell activation.

What two receptors are engaged during activation of naïve T cells?

TCR + CD28.

What coinhibitory molecule is upregulated on activated T cells?

CTLA-4.

What ligands does CTLA-4 bind?

The guide describes CTLA-4 as binding CD28 ligands, which produces an inhibitory effect.

What antibody in the study guide blocks CTLA-4?

Ipilimumab.

What happens when CTLA-4 engagement is blocked with ipilimumab?

The T cell can become reactivated.

What happens when a resting T cell recognizes antigen AND receives CD80/86 costimulation?

The T cell is activated and expands.

What happens when a T cell recognizes antigen on a non-APC but receives no costimulation?

The T cell becomes inactive/anergic.

What can happen if a T cell recognizes antigen but receives inhibitory rather than costimulatory signaling?

Anergy can occur.

Where does T-cell development occur?

Thymus.

What surrounds the thymus?

A capsule.

What divides the thymus into lobules?

Trabeculae.

What are the two main regions of a thymic lobule?

Outer = Cortex

Inner = Medulla

Where are immature T cells primarily located and developing?

Cortex.

What occurs in the thymic medulla?

The guide associates the medulla with negative selection and maturation and notes more macrophages and dendritic cells there.

What are immature T cells in the thymus called?

Thymocytes.

What does DN mean?

Double negative: neither CD4 nor CD8 is expressed.

What does DP mean?

Double positive: both CD4 and CD8 are expressed.

What does SP mean?

Single positive: the more mature cell has CD4 OR CD8.

What is a cTEC?

Cortical thymic epithelial cell, which helps with positive selection of developing T cells.

What is an mTEC?

Medullary thymic epithelial cell, which helps with negative selection by presenting self-antigens.

Which cells exclusively mediate positive selection according to the guide?

cTECs.

Can negative selection occur in both the cortex and medulla?

Yes.

Which stages can be targeted during negative selection?

DP and SP thymocytes.

Which thymic epithelial cells can present tissue-specific self-antigens according to the guide?

mTECs.

What is central selection?

Developing lymphocytes are selected in primary lymphoid organs to promote useful immune responses while limiting self-reactivity.

Is central tolerance perfect?

No. The guide says it is reinforced in the periphery, including by regulatory T cells.

What transcription/signaling factor is required for T-cell development according to the guide?

Notch1.

What does Notch1 promote according to the study guide?

T-cell rather than B-cell development.

Where do the earliest thymocytes enter the thymus?

Corticomedullary junction.

Where do thymocytes mature further after entering the thymus?

Thymic cortex.

Where do they finalize maturation?

Thymic medulla.

What does a TCR/CD4/MHC II signal favor?

CD4 single-positive cells.

After costimulation and activation, what helps determine T-cell function?

Signal 3 cytokines present during the response.

What Signal 3 cytokines are listed for TH1 differentiation?

IFN-γ, TNF, IL-12.

What Signal 3 cytokines are listed for TH2 differentiation?

IL-4 and IL-6.

What cytokines are listed for regulatory T cells?

TGF-β and IL-2.

What is the master transcription regulator for TH1 cells?

T-bet.

What is the master transcription regulator for TH2 cells?

GATA-3.

TH1/type 1 responses are broadly associated with what pathogens in the guide?

Bacteria and viruses.

TH2 responses are broadly associated with what pathogens?

Parasites/worms.

What STAT is associated with the TH1 pathway in the study guide's recall list?

STAT4.

What STAT is associated with the TH2 pathway in the study guide's recall list?

STAT6.

What is TH1/TH2 cross-regulation?

Regulation of the opposing T-helper pathway through transcription factors and cytokines.

What does T-bet suppress?

GATA-3 and TH2 cytokine production.

What does GATA-3 suppress?

T-bet and TH1 cytokines.

What happens to most effector T cells after pathogen clearance?

The guide states that at least 95% die by apoptosis, leaving a memory T-cell population.

How do memory T cells respond to a second challenge with the same antigen?

With heightened reactivity, producing a faster and more effective secondary response.

Naïve T cells are activated almost exclusively by what cells?

Dendritic cells.

Which APCs are listed as capable of activating memory T cells?

Macrophages, dendritic cells, and B cells.

What are the four memory T-cell subsets listed in the guide?

TCM: Central memory

TEM: Effector memory

TRM: Resident memory

TSCM: Stem cell memory

What can distinguish the different memory T-cell subsets?

Location, phenotype, and function.

What is the TCR?

A specialized surface receptor on T lymphocytes that recognizes specific antigens presented by MHC.

What is the basic structure of the TCR?

A heterodimer containing two polypeptide chains.

What are the two chains of the αβ TCR?

Alpha (α) and beta (β).

What regions are found in a TCR chain?

Variable domain

Constant domain

Transmembrane region

Cytoplasmic tail

What immunological structure does the TCR resemble?

Immunoglobulin/antibody.

What process generates diversity in TCR genes?

V(D)J recombination during T-cell development in the thymus.

Are all TCR genes located on one chromosome?

No.

What chromosome contains TCR α and δ genes?

Chromosome 14.

What chromosome contains TCR β and γ genes?

Chromosome 7.

What do V, D, J, and C stand for?

V = Variable

D = Diversity

J = Joining

C = Constant

What is the primary function of the TCR αβ heterodimer?

Recognizes antigen.

What is the function of the CD3 components associated with the TCR?

T-cell signaling.

What two main classes of TCR are listed?

αβ

γδ

Can the TCR bind antigen directly without antigen presentation?

No. The guide states that TCR requires antigen presentation by MHC.

What is the structure of MHC class I?

One large α chain

3 extracellular domains: α1, α2, α3

β2-microglobulin

What is the structure of MHC class II?

α chain: α1 and α2

β chain: β1 and β2

Which T cell recognizes antigen presented by MHC I?

CD8+ T cell.

Which T cell recognizes antigen presented by MHC II?

CD4+ T cell.

Is MHC class I expressed on epithelial cells?

Yes, according to the study guide.

Is MHC class I expressed on white blood cells?

Yes.

Do all cells express MHC class II according to the guide?

No.

What type of peptide does MHC class I typically present?

Cytosolic/intracellular peptide.

What type of peptide does MHC class II typically present?

Extracellular peptide.

What is the proteasome?

An intracellular system that degrades proteins into peptides.

What is an immunoproteasome?

A proteasome induced particularly by inflammatory cytokines such as IFN-γ that supports antigen processing and CD8 immune responses.

What can happen when a long peptide binds MHC class I?

The peptide may bulge out of the groove, be trimmed, or adopt another conformation.

What is the role of CLIP in MHC class II processing?

Prevents premature peptide binding to MHC class II in the endoplasmic reticulum.