Question 1

CD1-restricted T cells differ from other T cells restricted to class I or class II MHC molecules in which one of the following ways?
A)CD-1 restricted T cells cannot rapidly secrete cytokines.
B)CD-1 restricted T cells recognize non-peptide antigens, such as lipids.
C)CD-1 restricted T cells bind both cell-associated and soluble antigens.
D)CD-1 restricted T cells express both CD4 and CD8 coreceptors.
E)CD-1 restricted T cells are actually natural killer (NK) cells.

Accepted Answer

A small population of T cells express T cell receptors that recognize lipids bound to class I MHC-like molecules called CD1 molecules. These lipid antigen-specific T cells include CD4⁺CD8⁺, or CD4-CD8- αβ T cells. Many of these T cells also express markers found on natural killer (NK) cells and are therefore called NK T cells, although they are not actually NK cells. CD1-restricted T cells are still capable of rapidly producing cytokines such as IL-4 and IFN-ƴ, but their physiologic function is unknown.

Question 2

Selectins differ from integrins in which one of the following ways?
A)Selectins are expressed only on endothelial cells and integrins are expressed only on leukocytes.
B)Selectins are important mediators of leukocyte adhesion to endothelium, but integrins are not.
C)Selectins bind carbohydrate ligands, but integrins do not.
D)Selectins mediate rolling of leukocytes on endothelium, but integrins do not.
E)Selectins are a family of homologous molecules, but integrins are not.

Accepted Answer

Selectins specifically bind carbohydrate groups on cell surface glycoproteins, whereas integrins do not bind carbohydrate groups on Ig superfamily molecules. L-selectin and several integrins are both expressed on some lymphocytes. Both selectins and integrins are important mediators of leukocyte adhesion to endothelium. Both selectins and integrins (especially VLA-4) can mediate rolling interactions; selectins are more specialized in this regard. There are three members of the selectin family (E-, P-, and L-) and more than 30 different members of the integrin family.

Question 3

T cells may be important for recognition of common antigens at epithelial boundaries between the host and the external environment. The  T cells differ from the αβ T cells in which one of the following ways?
A)  T cells recognize only nonprotein antigens.
B)  T cells are not MHC-restricted and do not recognize MHC-associated antigens.
C)The  TCR complex contains CD3ƴ or CD3Ϭ but not CD3Ϭ.
D)Most mature  T cells express either CD4 or CD8 but not both.
E)  T cells lack key biologic activities, including the ability to lyse target cells.

Accepted Answer

T cells expressing the 11ea40f0_b579_0fe5_b42e_a90de8dc1811_TB1033_11 TCR are a lineage distinct from the much more numerous αβ-expressing T lymphocytes. The 11ea40f0_b579_0fe6_b42e_cf194ac7336e_TB1033_11 T cells do not recognize MHC-associated peptide antigens and are not MHC restricted. Some 11ea40f0_b579_0fe7_b42e_8dd53a4f0937_TB1033_11 T cells recognize protein or nonprotein antigens that do not require processing or particular types of antigen-presenting cells for their presentation. The 11ea40f0_b579_0fe8_b42e_27c641be2b5a_TB1033_11 heterodimer associates with the same CD3 and 11ea40f0_b579_0fe9_b42e_e938c4622d30_TB1033_11 proteins as do αβ receptors. Most 11ea40f0_b579_0fea_b42e_614791eb6b4e_TB1033_11 cells do not express CD4 or CD8. The 11ea40f0_b579_0feb_b42e_b5a1379b4bb8_TB1033_11 cells are capable of several biologic activities, including secretion of cytokines and lysis of target cells.

Question 4

A healthy 45-year-old child-care worker becomes infected with a virus and develops a sore throat, cough, and fever. Infected cells in the bronchial mucosa of this patient process virus-encoded proteins through an intracellular pathway and display peptides derived from the protein on the cell surface bound to class I MHC molecules. CD8⁺ T cells migrate to the mucosa and recognize these peptide-MHC complexes. Which of the following components of the TCR actually bind to the viral peptide-MHC complex?
A)Hypermutated regions: 1 in the α chain, 2 in the β chain
B)Complementarity-determining regions: 3 in the α chain, 3 in the β chain
C)Hypervariable regions: 2 in the α chain, 2 in the β chain
D)Congenic regions: 1 in the α chain, 1 in the β chain
E)One peptide-binding groove formed by the α chain and the β₂-microglobulin chain

Accepted Answer

Each α and β chain of the T cell receptor (TCR) contains both a constant and a variable domain. The variable domain contains short stretches of amino acids where the variability between different TCRs is concentrated, and these form the hypervariable or complementarity-determining regions (CDRs). Three CDRs in the α chain are juxtaposed to three similar regions in the β chain to form the part of the TCR that specifically recognizes peptide-MHC complexes. The variable regions of Ig molecules may undergo hypermutation during humoral immune responses, but this does not happen in TCRs. Congenic does not refer to a part of a protein, but rather to an inbred strain of animal. Peptide-binding grooves are part of MHC molecules, not TCRs.

Question 5

Most T lymphocytes have a dual specificity for which one of the following pairs of molecules?
A)A particular allelic form of a major histocompatibility complex (MHC) molecule and a peptide bound to the MHC molecule
B)Both MHC class I and class II molecules
C)Both peptide and glycolipid antigens
D)Both soluble peptides and peptide-MHC complexes
E)MHC molecules and CD4 or CD8

Accepted Answer

Most T cells are specific for polymorphic residues of a self major histocompatibility complex (MHC) molecule, which accounts for their MHC restriction, and for residues of a peptide antigen displayed by the MHC molecule, which accounts for antigen specificity. The receptor that recognizes peptide-MHC complexes is called the T cell receptor (TCR). Mature αβ T cells (the predominant type) express either CD4 or CD8, but not both. As such, each αβ T cell is restricted to bind either MHC class II or class I molecules, but not both. Although a small subset of T cells may recognize glycolipid antigens bound to class I MHC-like molecules called CD1, these T cells do not also recognize peptide antigens. Unlike the B cell receptor (immunoglobulins), the TCR can recognize only peptides displayed on MHC molecules, not soluble peptides alone. T cells express CD4 or CD8 and do not recognize CD4 or CD8 on other cells.

Question 6

CD44 expressed on the surface of T cells is critical for the binding of activated T cells to endothelium at sites of inflammation, and for the retention of T cells in extravascular tissues at sites of infection. CD44 does this by binding to which one of the following molecules?
A)VCAM-1
B)Hyaluronate
C)ICAM-1
D)Fibronectin
E)E-selectin

Accepted Answer

CD44 is a glycoprotein expressed on a variety of cells, particularly on recently activated and memory T cells. CD44 binds to hyaluronate, which allows for the retention of T cells in extravascular tissues at sites of infection and for the binding of activated and memory T cells to endothelium at sites of inflammation.

Question 7

LFA-1 is an integrin that promotes T cell activation by which one of the following mechanisms?
A)Binds to the α3 domain of class I MHC molecules, mediating high avidity between T cells and antigen-presenting cells (APCs)
B)Binds to B7-1 or B7-2 on the surface of APCs, mediating "signal 2"
C)Binds to GlyCAM-1 on high endothelial venules of lymph nodes, mediating rolling of T cells on endothelium
D)Binds to ICAM-1 on the surface of a variety of cells, mediating firm adhesion between T cells and APCs or endothelial cells
E)Binds to VCAM-1 on the surface of cytokine-activated endothelial cells, mediating homing of T cells to peripheral sites of inflammation

Accepted Answer

LFA-1 is an integrin expressed on the surface of leukocytes, which binds ICAM-1 to mediate specific, firm adhesion between T cells and antigen-presenting cells, as well as leukocytes and endothelial cells. As such, it plays an important role in the activation of T lymphocytes and in their migration to sites of infection and inflammation. In contrast, CD8 binds the α3 domain of class I MHC molecules, CD28 and CTLA-4 bind B7 proteins, L-selectin is the receptor for GlyCAM-1, and VLA-4 is the receptor for VCAM-1.

Question 8

After 2 years of hard work, a graduate student finally succeeds in creating a gene knockout mouse lacking CD4. The student is particularly careful to keep this mouse line in a microbe-free animal facility because these mice are expected to show:
A)No ability to produce IgM antibodies
B)Impaired ability to produce antibodies and activate macrophages
C)No ability to activate naive class I-restricted T cells
D)Complete absence of cytotoxic T lymphocyte (CTL) responses to viral infections
E)Failure to produce neutrophils

Accepted Answer

Knockout mice lacking CD4 do not contain mature class II-restricted T cells because the CD4 coreceptor plays an essential role in the maturation of T cells in the thymus. Most CD4⁺ class II-restricted T cells are cytokine-producing helper cells that function in host defense against intracellular microbes. These helper T cells are critical for activating B cells to produce antibodies, and for activating macrophages to efficiently kill phagocytosed microbes. Knockout mice lacking CD4 therefore do not have any helper T cells. IgM antibody production is generally not dependent on help from CD4⁺ T cells. Because CD8 is still expressed, naive class I-restricted T cells are still present and able to respond to intracellular infections, although this ability may be impaired by lack of T cell help. Neutrophil production by the bone marrow should be relatively normal.

Question 9

Both CD28 and CTLA-4 are receptors on T cells that are critical for regulating T cell activation. In which one of the following ways does CD28 differ from CTLA-4?
A)Only CD28 binds the costimulatory ligands B7-1 and B7-2 expressed on professional antigen-presenting cells.
B)CD28 counteracts positive, pro-proliferative T cell signals delivered by CTLA-4.
C)CD28 is constitutively expressed on naive T cells, whereas CTLA-4 is expressed on activated T cells.
D)CD28 binds its ligand with 10-fold greater affinity than does CTLA-4.
E)CD28 is important for delivering "signal 1" for T cell activation, whereas CTLA-4 is important for delivering "signal 2."

Accepted Answer

CD28 is constitutively expressed on more than 90% of CD4⁺ T cells and 50% of CD8⁺ T cells, whereas CTLA-4 is expressed only on activated T cells. Both B7-1 and B7-2, expressed on professional antigen-presenting cells (APCs), bind to both CD28 and CTLA-4 receptors on T cells. Binding of B7 molecules on APCs to CD28 delivers "positive" signals to the T cells that stimulate production of growth factors, promote T cell proliferation and differentiation, and induce expression of anti-apoptotic proteins. CTLA-4, however, functions to inhibit T cell activation by counteracting signals delivered by CD28. CTLA-4 also binds B7-1 with 10-fold greater affinity than CD28 binds B7-1; this difference may play an important role in the temporal sequence of T cell activation.

Question 10

The strength of integrin-dependent binding of T cells to antigen-presenting cells (APCs) may be rapidly increased by which one of the following mechanisms?
A)Integrin clustering and increased integrin affinity are induced by chemokines and antigen recognition.
B)Integrins stored in cytoplasmic organelles are mobilized to the T cell surface in response to TCR-mediated signals.
C)Integrin gene transcription is enhanced by chemokine-generated signals.
D)The affinity of integrin ligands on APCs is increased in response to chemokines.
E)Integrin ligands stored in cytoplasmic granules in the APCs are mobilized to the cell surface in response to CD40-CD40 ligand interaction.

Accepted Answer

T cell integrin affinity is enhanced by "inside-out signaling" in response to antigen binding to the T cell receptor (TCR) and chemokine binding to chemokine receptors. In addition, antigen and chemokines can induce clustering of integrins in the region of the T cell membrane in contact with the antigen-presenting cell (APC). These changes cause stronger T cell binding to APCs displaying the peptide-MHC complex that the T cell recognizes, thus ensuring prolonged T cell/APC contact and T cell activation. Integrins are not stored in cytoplasmic granules, and transcriptional activity cannot account for rapid changes in integrin-mediated binding. Integrin ligands (such as ICAM-1) do not undergo changes in affinity, nor are they stored in cytoplasmic granules.

Question 11

A 2-year-old boy suffers from recurrent bacterial infection of his ears, sinuses, lungs, and skin; laboratory studies indicate absence of sialylated Lewis X on his leukocytes. He is diagnosed with leukocyte adhesion deficiency type 2 (LAD-2). Which type of adhesive interaction required for leukocyte migration is defective in this boy?
A)E-selectin ligand binding to E-selectin
B)CD4 binding to class II MHC
C)VLA-4 binding to VCAM-1
D)Ig Fc receptor binding to Ig-coated cells
E)LFA-1 binding to ICAM-1

Accepted Answer

Leukocyte adhesion deficiency type 2 (LAD-2) is a rare genetic disorder characterized by severely impaired neutrophil rolling and adhesion to activated endothelium. The cause is a defect in the synthesis of sialylated Lewis X, the carbohydrate ligand on neutrophils and other leukocytes that is required for binding to E-selectin and P-selectin on cytokine-activated endothelium. In a clinically similar disorder called LAD-1, there is absent or deficient expression of the CD11CD18 family of integrins (of which LFA-1 is a member). Adhesion interactions mediated by CD4, Fc receptor, and VLA-4 are normal in patients with LAD-2.

Question 12

A 15-year-old girl develops malaise, headache, and low-grade fever, followed by pharyngitis and cervical lymph node enlargement as a result of infectious mononucleosis caused by Epstein-Barr virus (EBV). Her acute symptoms resolve within 2 weeks, and the fatigue improves within 3 months. Following the primary infection described in this patient, the patient's subsequent exposure to Epstein-Barr virus (EBV) will trigger clonal expansion of EBV-specific T cells expressing which one of the following surface molecules?
A)CD62Lʰᶦᵍʰ
B)CD44ˡᵒʷ
C)CD45RAʰᶦᵍʰ
D)CD45ROʰᶦᵍʰ
E)CD21ʰᶦᵍʰ

Accepted Answer

After primary infection, subsequent exposure to Epstein-Barr virus (EBV) (i.e., secondary infection) will trigger clonal expansion of EBV-specific memory T cells. Memory T cells express CD45RO. CD45RA is expressed on naive human T cells. CD62L, or L-selectin, is a peripheral lymph node homing receptor that is expressed at high levels on naive T lymphocytes but not on activated or memory T lymphocytes. CD44 is an adhesion molecule that is expressed at low levels on naive T lymphocytes and at high levels on activated and memory T lymphocytes. CD21 is actually the EBV receptor, but it is expressed on B cells (and follicular dendritic cells). It normally functions as a coreceptor to deliver activating signals in B cells.

Question 13

Which of the following is NOT a property shared by both CD4 and CD8?
A)Binds to nonpolymorphic regions of MHC molecules
B)Cytoplasmic tail associates with the Src family kinase Lck
C)Is a member of the Ig superfamily
D)Functions as a coreceptor for αβ TCRs
E)Is expressed on the majority of mature blood T cells

Accepted Answer

CD4 is expressed on the majority (~65%) of mature blood T cells, whereas CD8 is expressed on a minority (~35%). Both CD4 and CD8 are transmembrane glycoprotein members of the Ig superfamily, both serve as MHC-binding coreceptors for the T cell receptor, and both participate in early signal transduction events via cytoplasmic tail binding of the Src family tyrosine kinase Lck

Question 14

CD8 is a protein that functions as a coreceptor for a subset of T cells and plays a significant role in all of the following EXCEPT:
A)Recognition of peptide antigen bound to class I MHC molecules
B)Maturation of MHC class I-restricted T cells
C)Infection of T cells by human immunodeficiency virus (HIV)
D)Signaling via Lck tyrosine kinase to initiate T cell activation
E)Strengthening the binding of T cells to antigen-presenting cells, albeit with low affinity

Accepted Answer

CD4, but not CD8, serves as a receptor for the human immunodeficiency virus (HIV). CD8 is a coreceptor that binds to class I MHC molecules. It is expressed on T cells whose T cell receptors (TCRs) recognize complexes of peptide and class I MHC molecules. CD8 plays a critical role in the maturation of class I MHC-restricted T cells in the thymus because this process requires the maturing T cells to recognize class I MHC on thymic antigen-presenting cells (APCs). Both CD8 and CD4 associate with the Src family tyrosine kinase, called Lck, and thus they participate in the early signal transduction events that occur after T cell recognition of peptide-MHC complexes on APCs. The affinities of CD8 and CD4 for MHC molecules are very low, but they are still thought to play some role in mediating adhesion between T cells and APCs.

Question 15

Neonates, elderly persons, and otherwise immunocompromised patients are particularly susceptible to infections with Listeria monocytogenes. These patients typically have fever and chills, often progressing to hypotension and septic shock. In healthy individuals, however, such intracellular microbes are usually effectively phagocytosed and killed by macrophages, which become activated via:
A)CD40L-CD40 interactions between activated T helper cells and macrophages
B)CD28-B7 interactions between activated T cells and macrophages
C)Fas ligand-Fas interactions between activated cytotoxic T lymphocytes and macrophages
D)TCR-MHC class II interactions between activated T helper cells and macrophages
E)LFA-1-ICAM-1 interactions between activated T cells and macrophages

Accepted Answer

Activated CD4⁺ T cells express CD40 ligand (CD40L), which binds to CD40 on B lymphocytes, macrophages, dendritic cells, and endothelial cells thereby activating these cells. Only activated macrophages can effectively phagocytose and kill intracellular microbes such as Listeria. CD28-B7 and TCR-MHC class II interactions provide signals 2 and 1, respectively, in the activation of T cells by antigen-presenting cells (not the activation of macrophages by T cells). Engagement of Fas by Fas ligand (FasL) on T cells results in apoptosis and provides one of the mechanisms by which CTLs kill their targets. LFA-1-ICAM-1 mediates cell adhesion interactions important in T cell activation and homing.

Question 16

A 15-year-old girl develops malaise, headache, and low-grade fever, followed by pharyngitis and cervical lymph node enlargement as a result of infectious mononucleosis caused by Epstein-Barr virus (EBV). Her acute symptoms resolve within 2 weeks, and the fatigue improves within 3 months. All of the following are required for CD8⁺ cytotoxic T lymphocyte (CTL) recognition and killing of EBV-infected cells EXCEPT:
A)β₂-Microglobulin
B)HLA-A, -B or -C
C)CD28
D)LFA-1 (leukocyte function-associated antigen-1)
E)TAP (transporter associated with antigen processing)

Accepted Answer

CD28 is not involved in antigen recognition by T cells, but rather, in costimulation. Cell-mediated immunity against intracellular organisms, such as viruses, is largely mediated by class I-restricted T cells, such as cytotoxic T lymphocytes (CTLs). The class I MHC molecules are HLA-A, HLA-B, and HLA-C. CTLs recognize complexes of viral peptides with class I MHC molecules. β₂-Microglobulin is the nonpolymorphic, noncovalently associated polypeptide chain of MHC class I molecules. TAP is a critical protein involved in the processing and presentation of antigen by class I MHC. LFA-1 is an important integrin mediating adhesion of the CD8⁺ T cells to virus-infected target cells.

Question 17

The T cell receptor (TCR) complex differs from an immunoglobulin molecule in which one of the following ways?
A)On average, a TCR binds antigen with much lower affinity than does an Ig molecule.
B)The TCR can serve as a lymphocyte antigen receptor, but an Ig molecule cannot.
C)Only the TCR can bind soluble antigen directly.
D)The TCRs expressed by one clone of T cells can undergo changes in constant region structure after cellular activation, whereas Ig molecules expressed by one clone of B cells do not.
E)The TCR polypeptide chains have short cytoplasmic tails and rely on associated proteins for signaling functions, whereas membrane Ig receptors are competent signaling molecules on their own.

Accepted Answer

TCRs bind antigen with much lower affinity than immunoglobulins (the dissociation constant for the TCR is 10-⁵ to 10-⁷ versus 10-⁷ to 10-¹¹ for secreted Ig). Both T cell receptors (TCRs) and membrane Ig serve as lymphocyte antigen receptors on T cells and B cells, respectively. TCRs do not bind soluble antigens, but rather cell surface-associated peptide-MHC molecule complexes. Only immunoglobulins undergo constant region changes, called heavy chain isotype switching. Both TCRs and Ig have short cytoplasmic tails and rely on associated signaling molecules (CD3 and 11ea40f0_b578_c1bd_b42e_b7b01a9126a4_TB1033_11 for TCR, Igα and Igβ for membrane Ig).-

Quiz 4: Antigen Recognition in the Adaptive Immune System

CD1-restricted T cells differ from other T cells restricted to class I or class II MHC molecules in which one of the following ways?

Selectins differ from integrins in which one of the following ways?

T cells may be important for recognition of common antigens at epithelial boundaries between the host and the external environment. The T cells differ from the αβ T cells in which one of the following ways?

Most T lymphocytes have a dual specificity for which one of the following pairs of molecules?

CD44 expressed on the surface of T cells is critical for the binding of activated T cells to endothelium at sites of inflammation, and for the retention of T cells in extravascular tissues at sites of infection. CD44 does this by binding to which one of the following molecules?

LFA-1 is an integrin that promotes T cell activation by which one of the following mechanisms?

After 2 years of hard work, a graduate student finally succeeds in creating a gene knockout mouse lacking CD4. The student is particularly careful to keep this mouse line in a microbe-free animal facility because these mice are expected to show:

Both CD28 and CTLA-4 are receptors on T cells that are critical for regulating T cell activation. In which one of the following ways does CD28 differ from CTLA-4?

The strength of integrin-dependent binding of T cells to antigen-presenting cells (APCs) may be rapidly increased by which one of the following mechanisms?

Which of the following is NOT a property shared by both CD4 and CD8?

CD8 is a protein that functions as a coreceptor for a subset of T cells and plays a significant role in all of the following EXCEPT:

The T cell receptor (TCR) complex differs from an immunoglobulin molecule in which one of the following ways?