Test bank for the immune system 4th edition by parham

5–6 Unlike the C regions of immunoglobulin heavy-chain loci, the C regions of the T-cell receptor β-chain loci 1.. trims peptides to fit MHC class I molecules 5–26 Discuss how T-cell re

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CHAPTER 5: ANTIGEN RECOGNITION BY T LYMPHOCYTES

5–1 T cells recognize antigen when the antigen

1 forms a complex with membrane-bound MHC molecules on another derived cell

host-2 is internalized by T cells via phagocytosis and subsequently binds to T-cell receptors in the endoplasmic reticulum

3 is presented on the surface of a B cell on membrane-bound immunoglobulins

4 forms a complex with membrane-bound MHC molecules on the T cell

5 bears epitopes derived from proteins, carbohydrates, and lipids

5–2 T-cell receptors structurally resemble

1 the Fc portion of immunoglobulins

of the following is inconsistent with experimental data?

1 The highly variable CDR loops are located across the top surface

2 The membrane-proximal domains consist of Cα and Cβ

3 The portion that makes physical contact with the ligand comprises Vβand Cβ, the domains farthest from the T-cell membrane

4 The transmembrane regions span the plasma membrane of the T cell

5 The cytoplasmic tails of the T-cell receptor α and β chains are very short

5–4 Unlike B cells, T cells do not engage in any of the following processes except

1 alternative splicing to produce a secreted form of the T-cell receptor

2 alternative splicing to produce different isoforms of the T-cell receptor

1 the T-cell receptor α locus differs because it has embedded within its

sequence another locus that encodes a different type of T-cell receptor chain

2 both are encoded on chromosome 14

3 the T-cell receptor α-chain locus does not contain D segments

4 the T-cell receptor α-chain locus contains more V and J regions

5 the T-cell receptor α-chain locus contains more C regions

6 they both contain exons encoding a leader peptide

5–6 Unlike the C regions of immunoglobulin heavy-chain loci, the C regions of the T-cell receptor β-chain loci

1 are functionally similar

2 do not contain D segments

3 are more numerous

4 are encoded on a different chromosome from the variable β-chain gene

segments of the T-cell receptor

5 do not encode a transmembrane region

6 possess non-templated P and N nucleotides

5–7 Which of the following statements regarding Omenn syndrome is incorrect?

1 A bright red, scaly rash is due to a chronic inflammatory condition

2 Affected individuals are susceptible to infections with opportunistic

pathogens

3 It is invariably fatal unless the immune system is rendered competent

through a bone marrow transplant

4 It is the consequence of complete loss of RAG function

5 There is a deficiency of functional B and T cells

6 It is associated with missense mutations of RAG genes

5–8

1 Identify which features of the RAG genes have similarity to the transposase

gene of transposons

2 Explain how the mechanisms for immunoglobulin and T-cell receptor

rearrangement may have evolved in humans

5–9 All of the following statements regarding γ:δ T cells are correct except

1 they are more abundant in tissue than in the circulation

2 the δ chain is the counterpart to the β chain in α:β T-cell receptors because it contains V, D, and J segments in the variable region

3 they share some properties with NK cells

4 activation is not always dependent on recognition of a peptide:MHC molecule complex

5 expression on the cell surface is not dependent on the CD3 complex

5–10 Match the term in Column A with its complement in Column B

_a T-cell receptor

δ-chain gene 1 positioned in the T-cell receptor α-chain locus

between Vα and Jα gene segments

_b CD3 complex 2 made up of γ, δ and ε

components

_c T-cell receptor

β-chain gene 3 located on chromosome 7

_d CD4 4 counterpart to the

T-cell receptor α-chain gene

_e T-cell receptor

γ-chain gene 5 four extracellular domains

5–11 During T-cell receptor _-gene rearrangement, two D segments may be used in the final rearranged gene sequence, thereby increasing overall variability of this chain

5–12 The degradation of pathogen proteins into smaller fragments called peptides

is a process commonly referred to as

5–13 All of the following are primarily associated with CD4 T-cell function except

1 improve phagocytic mechanisms of tissue macrophages

2 assist B cells in the production of high-affinity antibodies

3 kill virus-infected cells

4 facilitate responses of other immune-system cells during infection

5 assist macrophages in sustaining adaptive immune responses through their secretion of cytokines and chemokines

5–17 Which of the following is not a characteristic of immunoproteasomes?

1 They make up about 1% of cellular protein

2 They consist of four rings of seven polypeptide subunits that exist in

alternative forms

3 They are produced in response to IFN-γ produced during innate immune responses

4 They produce a higher proportion of peptides containing acidic amino acids

at the carboxy terminus compared with constitutive proteasomes

5 They contain 20S proteasome-activation complexes on the caps

5–18 Identify which of the following statements is true regarding the transporter associated with antigen processing (TAP)

1 TAP is a homodimer composed of two identical subunits

2 TAP transports proteasome-derived peptides from the cytosol directly to the lumen of the Golgi apparatus

3 TAP is an ATP-dependent, membrane-bound transporter

4 Peptides transported by TAP bind preferentially to MHC class II molecules

5 TAP deficiency causes a type of bare lymphocytes syndrome resulting in severely depleted levels of MHC class II molecules on the surface of antigen-presenting cells

5–20 Which of the following best describes the function of tapasin?

1 Tapasin is an antagonist of HLA-DM and causes more significant increases in MHC class I than MHC class II on the cell surface

2 Tapasin is a lectin that binds to sugar residues on MHC class I molecules, cell receptors, and immunoglobulins and retains them in the ER until their subunits have adopted the correct conformation

T-3 Tapasin is a thiol-reductase that protects the disulfide bonds of MHC class I molecules

4 Tapasin participates in peptide editing by trimming the amino terminus of peptides to ensure that the fit between peptide and MHC class II molecules is appropriate

5 Tapasin is a bridging protein that binds to both TAP and MHC class I

molecules and facilitates the selection of peptides that bind tightly to MHC class I molecules

2 cathepsin S-mediated cleavage of invariant chain

3 the participation of tapasin in finding a ‘good fit’ for class I heterodimers

4 recycling an MHC class I heterodimer if the peptide falls out of its binding groove

peptide-5 upregulation of HLA-DM by interferon-γ

_d receptor-mediated

endocytosis 4 removes class II-associated invariant-chain

peptide (CLIP) _e ERp57 5 internalization of

immunoglobulin:antigen complexes by B cells

_f HLA-G 6 expressed only by

extravillous trophoblasts

_g HLA-F 7 trims peptides to fit

MHC class I molecules

5–26 Discuss how T-cell receptors differ from immunoglobulins in the way that they recognize antigen Use the following terms in your answer: peptides, antigen-presenting cells, MHC molecules, and antigen-binding sites

2 Repeat this for the classes of T cells that are stimulated by extracellular

pathogens For the purposes of this question, count those pathogens (such as mycobacteria) that can survive and live inside intracellular vesicles after being taken up by macrophages as extracellular pathogens

4 carbohydrate and lipid

5 carbohydrate, lipid, and protein

5–29 Indicate whether each of the following statements regarding T cells is true (T) or false (F)

1 T cells and B cells recognize the same types of antigen

2 T cells and B cells require MHC molecules for the recognition of peptide antigens

3 T cells require an accessory cell called an antigen-presenting cell, which bears MHC molecules on its surface

4 T-cell receptor and immunoglobulin genes are encoded on the MHC

5 The T-cell receptor has structural similarity to an immunoglobulin Fab fragment

3 Class switching enables a change in effector function

4 The antigen receptor is composed of two identical heavy chains and two identical light chains

5 Carbohydrate, lipid, and protein antigens are recognized and stimulate a response

5–31 The antigen-recognition site of T-cell receptors is formed by the association

of which of the following domains?

5–34 IgG possesses _ binding sites for antigen, and the T-cell receptor

possesses _ binding sites for antigen:

1 1; 1

2 2; 1

3 1; 2

1 λ light chain; κ light chain

2 heavy chain; λ light chain

3 κ light chain; heavy chain

4 λ light chain; heavy chain

5 κ light chain; λ light chain

5–37 Owing to the location of the δ-chain locus of the T-cell receptor on

chromosome 14, if the _-chain locus rearranges by somatic recombination, then the δ-chain locus is _:

5–38 Explain how professional antigen-presenting cells optimize antigen

presentation to T cells despite the relatively limited capacity of any particular MHC molecule to bind different pathogen-derived peptides

5–39 Which of the following is not a characteristic of native antigen recognized by

T cells?

1 peptides ranging between 8 and 25 amino acids in length

2 not requiring degradation for recognition

3 amino acid sequences not found in host proteins

4 primary, and not secondary, structure of protein

5 binding to major histocompatibility complex molecules on the surface of antigen-presenting cells

5–40 Which of the following statements regarding CD8 T cells is incorrect?

1 When activated, CD8 T cells in turn activate B cells

2 CD8 is also known as the CD8 T-cell co-receptor

3 CD8 binds to MHC molecules at a site distinct from that bound by the T-cell receptor

4 CD8 T cells kill pathogen-infected cells by inducing apoptosis

5 CD8 T cells are MHC class I-restricted

5–41 Antigen processing involves the breakdown of protein antigens and the subsequent association of peptide fragments on the surface of antigen-presenting cells with

1 α:β T-cell receptors recognize antigen only as a peptide bound to an MHC molecule

2 αβ T-cell receptors recognize antigens in their native form

3 α:β T-cell receptors, like B-cell immunoglobulins, can recognize carbohydrate, lipid, and protein antigens

4 Antigen processing occurs in extracellular spaces

5 Like α:β T cells, γ:δ T cells are also restricted to the recognition of antigens presented by MHC molecules

4 all of the above

5 none of the above

5–44 MHC class II molecules are made up of two chains called _, whose

function is to bind peptides and present them to _ T cells:

1 alpha (α) and beta (β); CD4

2 alpha (α) and beta2-microglobulin (β2m); CD4

3 alpha (α) and beta (β); CD8

4 alpha (α) and beta2-microglobulin β2m); CD8

5 alpha (α) and beta (β); γ:δ T cells

3 membrane-proximal domains of the MHC molecule

4 constant regions of antibody molecules

5 α helices of the MHC molecule

5–46 The CDR3 loops of the T-cell receptor contact the _:

1 side chains of amino acids in the middle of the peptide

2 co-receptors CD4 or CD8

3 membrane-proximal domains of the MHC molecule

4 constant regions of antibody molecules

5 α helices of the MHC molecule

1 a particular MHC molecule has the potential to bind to different peptides

2 when MHC molecules bind to peptides, they are degraded

3 peptides bind with low affinity to MHC molecules

4 none of the above describes promiscuous binding specificity

3 phagolysosome-derived peptides bind to MHC class II molecules

4 peptides of nuclear or cytosolic proteins are presented by MHC class II

molecules

5–53 In reference to the interaction between T-cell receptors and their

corresponding ligands, which of the following statements is correct?

1 The organization of the T-cell receptor antigen-binding site is distinct from the antigen-binding site of immunoglobulins

2 The orientation between T-cell receptors and MHC class I molecules is

different from that of MHC class II molecules

3 The CDR3 loops of the T-cell receptor α and β chains form the periphery of the binding site making contact with the α helices of the MHC molecule

4 The most variable part of the T-cell receptor is composed of the CD3 loops of both the α and β chains

5 All of the above statements are correct

5–54 The diversity of MHC class I and II genes is due to _ (Select all that apply.)

1 gene rearrangements similar to those observed in T-cell receptor genes

2 the existence of many similar genes encoding MHC molecules in the genome

5–58 Of the following HLA α-chain loci, which one exhibits the highest degree of polymorphism?

5–59 Which of the following are not encoded on chromosome 6 in the HLA

complex? (Select all that apply.)

5–61 Peptides that bind to a particular MHC isoform usually have either the same

or chemically similar amino acids at two to three key positions that hold the peptide tightly in the peptide-binding groove of the MHC molecule These amino acids are called _ and the combination of these key residues is known as its _

5 restriction residues; MHC allotype

_b cross-presentation 2 evolutionary

maintenance of divergent MHC molecule phenotypes

_c heterozygote

advantage 3 recognition of peptide antigen by a given

T-cell receptor when bound

to a particular MHC allotype

_d balancing selection 4 mechanism used to

increase polymorphisms of HLA class I and class II alleles involving

homologous recombination between different alleles of the same gene

_e interallelic

conversion 5 presentation of a wider range of peptides

when MHC isotypes inherited from each parent are different

5–64 Directional selection is best described as

1 all polymorphic alleles preserved in a population

2 T-cell receptor interaction with peptide:MHC complexes directed to a planar interface

3 a mechanism in T cells that is analogous to affinity maturation of

immunoglobulins

4 selected alleles increase in frequency in a population

5 selection of most appropriate transplant donor directed at the identification

of identical or similar combinations of HLA alleles compared with the

transplant recipient

5–65 Describe (A) five ways in which T-cell receptors are similar to

immunoglobulins, and (B) five ways in which they are different (other than the way

in which they recognize antigen)

5–66 Compare the organization of T-cell receptor α and β genes (the TCRα and TCRβ loci) with the organization of immunoglobulin heavy-chain and light-chain genes

1 transduce signals to the interior of the T cell

2 bind to antigen associated with MHC molecules

1 CD8; virus-infected cells; kill virus-infected cells

2 CD8; B cells; stimulate B cells to differentiate into plasma cells

3 CD4; macrophages; enhance microbicidal powers of macrophages

4 CD4; B cells; stimulate B cells to differentiate into plasma cells

5 All of the above are accurate

5–70 The immunological consequence of severe combined immunodeficiency

disease (SCID) caused by a genetic defect in either RAG-1 or RAG-2 genes is

1 lack of somatic recombination in T-cell receptor and immunoglobulin gene loci

2 lack of somatic recombination in T-cell receptor loci

3 lack of somatic recombination in immunoglobulin loci

4 lack of somatic hypermutation in T-cell receptor and immunoglobulin loci

5 lack of somatic hypermutation in T-cell receptor loci

5–71

1 (i) Describe the structure of an MHC class I molecule, identifying the different polypeptide chains and domains (ii) What are the names of the MHC class I molecules produced by humans? Which part of the molecule is encoded within the MHC region of the genome? (iii) Which domains or parts of

domains participate in the following: antigen binding; binding the T-cell receptor; and binding the T-cell co-receptor? (iv) Which domains are the most polymorphic?

2 Repeat this for an MHC class II molecule

5–72 What is meant by the terms (A) antigen processing and (B) antigen

presentation? (C) Why are these processes required before T cells can be activated?

2 What would be the outcome (i) if invariant chain were defective or missing,

or (ii) if HLA-DM were not expressed?