Homework 3: Antigen Recognition by T Lymphocytes and B Cell Development

The diversity of MHC class I and II genes is due to ___________.

- gene rearrangement similar to those observed in T-cell receptor genes - the existence of many similar genes encoding MHC molecules in the genome with extensive polymorphism

An important advantage of having two gene loci (κ and λ) for the light chain is...

...that the likelihood of a successful rearrangement of light chain genes increases.

IgG possesses ___ binding sites for antigen, and the T-cell receptor possesses ___ binding sites for antigens.

2 1

How many complementary-determining regions contribute to the antigen binding site in an intact T-cell receptor?

6

When comparing the T-cell receptor \alpha-chain locus with the immunoglobulin heavy-chain locus, all of the following are correct except a. the T-cell receptor \alpha locus differs because it has embedded within its sequence another locus that encodes a different type of T-cell receptor chain b. both are encoded on chromosome 14 c. the T-cell receptor \alpha-chain locus does not contain D segments d. the T-cell receptor \alpha-chain contains more V and J regions e. the T-cell receptor \alpha-chain contains more C regions

?

Negative selection of developing B cells ensures that ____________.

???

Which of the following do not associate with on another during B-cell development? a. IL-7 : IL-7 receptor of late pro-B cells b. Pax-5 : CD19 gene c. surrogate light chain : δ heavy chain d. VpreB : λ5 e. SCF : Kit f. pre-B-cell receptor : Igα and Igβ

???

A defect in which of the following proteins block B-cell development at the pre-B-cell stage, resulting in almost no circulating antibodies in individuals with this defect?

Bruton's tyrosine kinase (Btk)

All hematopoietic stem cells express ________.

CD34

Which cell-surface marker differentiates hematopoietic stem cells from other cell constituents in the bone marrow?

CD34

In B cells, transport of immunoglobulin to the membrane is dependent on association with two invariant proteins, Igα and Igβ. Which invariant protein provides this function for the T-cell receptor in T-cells?

CD3γ CD3δ CD3ϵ ζ

What is the fate of an immature B cell that encounters and has specificity for self antigen?

Continued rearrangement of light-chain genes.

The combination of all HLA class I and class II allotypes that an individual expresses is referred to as their ______________.

HLA type

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

MHC class I or class II molecules

The primary reason for transplant rejections is due to differences in _____ between donor and recipient.

MHC molecules

The proto-oncogene ______ is associated with the development of Burkitt's lymphoma.

Myc

What is the function of tapasin?

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.

When the expression of __________ is turned off in small pre-B cells, the results in the presence of P nucleotides but an absence of N nucleotides in around 50% of light chain genes.

TdT

What is the reason that HIV-infected people with heterozygous HLA loci have a delayed progrssion to AIDS compared with patients who are homozygous at one or more HLA loci?

The greater number of HLA alleles provides a wider variety of HLA molecules for presenting HIV-derived peptides to CD8 T cells even if HIV mutates during the course of infect.

What is a characteristic of B-2 cells?

They are located primarily in secondary lymphoid organs.

The most variable part of the T-cell receptor are ____ and ____.

V(\alpha) V(\beta)

The antigen-recognition site of T-cell receptors is formed by the association of what two domains?

V(\alpha) and V(\beta)

Name a characteristic of a large pre-B cell.

VDJ is successfully rearranged and μ heavy chain is made.

The latest stages of late pro-B cell development are recognized by the association of a surrogate light chain with a μ chain. The surrogate light chain is composed of _____________.

VpreB and λ5

During T-cell receptor ___-gene rearrangement, two D segments may be using in final rearranged gene sequence, thereby increasing overall variability of this chain.

\delta

MHC molecules have promiscuous binding specificity. This means that:

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

Which of the following characteristics is common to both T-cell receptors and immunoglobulin? a. Somatic recombination of V, D, and J segments is responsible for the diversity of antigen-binding sites. b. Somatic hypermutation changes the affinity-binding sites and contributes to diversification. c. Class switching enables a change in effector function. d. The antigen receptor composed of two identical heavy chains and two identical light chains. e. Carbohydrate, lipids, and protein antigens are recognized and stimulate a response.

a. Somatic recombination of V, D, and J segments is responsible for the diversity of antigen-binding sites.

All of the following participate in signal transduction in developing B cells except a. TdT b. FLT3 c. CD19 d. Igα and Igβ e. Bruton's tyrosine kinase (Btk) f. CD45

a. TdT

Which of the following statements regarding CD8 T cells is incorrect? a. When activated, CD8 T cells in turn activate B cells b. CD8 is also known as the CD8 T-cell co-receptor c. CD8 binds to MHC molecules at a site distinct from that bound by the T-cell receptor d. CD8 T cells kill pathogen-infected cells by inducing apoptosis e. CD8 T cells are MHC class I- restricted.

a. When activated, CD8 T cells in turn activate B cells

All of the following occur within germinal centers except a. centrocytes mature from centroblasts b. isotype switching c. centroblasts arise from activated B cells d. B cells are activated by CD4 helper T cells e. affinity maturation f. somatic hypermutation g. production of memory B cells

a. centrocytes mature from centroblasts

When describing the various components of the vesicular system, which of the following is not included? a. nucleus b. Golgi apparatus c. endoplasmic reticulum d. exocytic vesicles e. lysosomes

a. nucleus

Plasma cells have all of the properties listed except a. they rapidly proliferate in secondary lymphoid follicles b. they secrete antibody c. they are terminally differentiated B cells d. they no longer express MHC class II molecule e. they cease expressing membrane-bound immunoglobulin f. they differentiate into plasma cells after migration from germinal centers to other sites in lymphoid tissues and bone marrow

a. they rapidly proliferate in secondary lymphoid follicles

Which of the following statements regarding T-cell recognition of antigen is correct? a. α:β T-cell receptors recognize antigen only as a peptide bound to an MHC molecule. b. α:β T-cell receptors recognize antigens in their native form. c. α:β T-cell receptors, like B-cell immunoglobulin, can recognize carbohydrate, lipid, and protein antigens. d. Antigen processing occurs in extracellular spaces. e. Like α:β T cells, γ:δ T cells are also restricted to the recognition of antigens presented by MHC molecules.

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

MHC class II molecules are made up of two chains called _________, whose function is to bind peptides and present them to _________ T cells.

alpha (α) and beta (β) CD4

Peptides that bind to a particular MHC isoform usually have either the same or chemically similar amino acids at two or three key positions that hold the peptide tightly in the peptide-binding groove on the MHC molecule. These amino acids are called __________ and the combination of these key residues is known as its __________.

anchor residues peptide-binding motif

The degradation of pathogen proteins into smaller fragments called peptides is a process commonly referred to as _________.

antigen processing

A developing B cell unable to generate a productive rearrangement on any of the four light-chain loci will undergo __________.

apoptosis

Unlike the C regions of immunoglobulin heavy-chain loci, the C region of the T-cell receptor \beta-chain loci ________.

are functionally similar

All of the following are included in the peptide-loading complex except a. tapasin b. calnexin c. calreticulin d. ERp57 e. \beta(2)-microglobulin

b. calnexin

Which of the following cell types is not considered a profession antigen-presenting cell? a. macrophage b. neutrophil c. B cell d. dendritic cell e. all of the above are professional antigen-presenting cells

b. neutrophils p. 132

Which of the following is not a characteristic of native antigen recognized by T cells? a. peptides ranging between 8 and 25 amino acids in length b. not requiring degradation for recognition c. amino acid sequences not found in host proteins d. primary, and not secondary, structure of protein e. binding MHC molecules on the surface of antigen-presenting cells

b. not requiring degradation for recognition

Which of the following does not contribute to the mechanisms of peptide editing? a. removal of amino acids from the amino-terminal end by ER aminopeptidase (ERAP) b. upregulation of HLA-DM by interferon-\gamma c. the participation of tapasin in finding a 'good fit' for class I heterodimers d. recycling MHC class I heterodimer if the peptide falls out of its peptide-binding groove

b. upregulation of HLA-DM by interferon-\gamma

The circulatory route through a lymphoid tissue for both immature B cells and mature B cells that do not encounter specific antigen is:

bloodstream → afferent lymphatic vessel → HEV of lymphoid cortex → efferent lymphatic vessel

All of the following are associated with the development of Burkitt's lymphoma except a. The expression of Myc protein is perturbed b. A chromosomal translocation involving a proto-oncogene and an immunogloblin gene occurs. c. Overproduction of the Bcl-2 protein prolongs the lifetime of B-lineage cells. d. Cell division restraints on mutated B cells are lifted. e. In addition to a chromosomal translocation event, mutations elsewhere in the genome are usually involved.

c. Overproduction of the Bcl-2 protein prolongs the lifetime of B-lineage cells.

Indicate which of the following statements regarding T cells is true. a. T cells and B cells recognize the same types of antigen. b. T cells and B cells require MHC molecules for the recognition of peptide antigens. c. T cells require an accessory cell called an antigen-presenting cell, which bears MHC molecules on its surface. d. T-cell receptor and immunoglobulin genes are encoded on the MHC. e. The T-cell receptor has structural similarity to an immunoglobulin Fc fragment.

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

Identify which of the following statements is true regarding the transported associated with antigen processing (TAP). a. TAP is a homodimer composed of two identical subunits. b. TAP transports proteasome-derived peptides from the cytosol directly to the lumen of the Golgi apparatus. c. TAP is an ATP-dependent, membrane-bound transporter. d. Peptides transported by TAP bind preferentially to MHC class II molecules. e. 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.

c. TAP is an ATP-dependent, membrane-bound transporter.

If viewing the three-dimension structure of a T-cell receptor from the side, with the T-cell membrane at the bottom and the receptor pointing upwards, which of the following is inconsistent with experimental data? a. The highly variable CDR loops are located across the top surface. b. The membrane-proximal domains consist of C(\alpha) and C(\beta). c. The portion that makes physical contact with the ligand comprises V(\beta) and C(\beta). d. The transmembrane regions span the plasma membrane of the T cell. e. The cytoplasmic tails of the T-cell receptor \alpha and \beta chains are very short.

c. The portion that makes physical contact with the ligand comprises V(\beta) and C(\beta).

Which of the following statements about the IgD made by B cells of upper respiratory mucosa is not true? a. These antibodies bind to airborne bacteria such as Haemophilus influenzae. b. λ light chains are used almost exclusively bu these IgD antibodies. c. Two-thirds of these IgD antibodies possess κ light chains. d. These IgD antibodies recruit basophils and induce the secretion of antibacterial peptides.

c. Two-thirds of these IgD antibodies possess κ light chains.

All of the dollowing are primarily associated with CD4 T-cell function except a. improve phagocytic mechanisms of tissue macrophages b. assist B cells in the production of high-affinity antibodies c. kill virus-infected cells d. facilitate responses of other immune-system cells during infection e. assist macrophages in sustaining adaptive immune responses through their secretion of cytokines and chemokines

c. kill virus-infected cells

Immunological tolerance in the B-cell repertoire is called _____ tolerance when it develops in primary lymphoid organs, and _____ tolerance when it is induced outside the bone marrow.

central peripheral

Identify the mismatched pair of chemokine and the cells that secrete it. a. CCL19 : lymph-node dendritic cells b. CXCL13 : follicular dendritic cells c. CCL21 : stromal cells of secondary lymphoid tissues d. All of the above are correctly matched.

d. All of the above are correctly matched.

Which of the following statements regarding Omenn syndrome is incorrect? a. A bright red, scaly rash is due to chronic inflammatory condition. b. Affected individuals are susceptible to infections with opportunistic pathogens. c. It is invariably fatal unless the immune system is rendered competent through a bone marrow transplant. d. It is the consequence of complete loss of RAG function. e. There is a deficiency of functional B and T cells.

d. It is the consequence of complete loss of RAG function. Figure 5.4 - Omenn syndrome is cause by "a mutation in a Rag gene" which "reduces RAG activity by 80%." SCID is the consequence of complete loss of RAG function.

Individuals who fail to express functional Bruton's tyrosine kinase exhibit all of the following characteristics except a. B-cell development is blocked at the immature B-cell stage. b. They are usually male because the Btk gene is on the X chromosome. c. They suffer from an immune deficiency known as X-linked agammaglobulemia (XLA). d. Recurrent infections with extracellular bacteria are common. e. They benefit from treatment with immunoglobulin infusions.

d. Recurrent infections with extracellular bacteria are common.

In reference to the interaction between T-cell receptors and their corresponding ligands, which of the following statements is correct? a. The organization of T-cell receptor antigen-binding site is distinct from the antigen binding site of immunoglobulin. b. The orientation between T-cell receptors and MHC class I molecules is different from that of MHC class II molecules. c. 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. d. The most variable part of the T-cell receptor is composed of the CD3 loops of both the α and β chains. e. All of the above statements are correct.

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

Which of the following is not characteristic of immunoproteasomes? a. They make up about 1% of cellular protein b. They consist of four rings of seven polypeptide subunits that exist in alternative forms. c. They are produced in response to IFN-\gamma produced during innate immune responses. d. The produce a higher proportion of peptides containing acidic amino acids at the carboxy terminus compared with constitutive proteasomes. e.They contain 20S proteasome-activation complexes on the caps.

d. The produce a higher proportion of peptides containing acidic amino acids at the carboxy terminus compared with constitutive proteasomes.

What characterized the B-cell that develops prenatally? a. They lack N nucleotides. b. They possess polyspecificity for bacterial polysaccharide antigens. c. They arise early in embryonic development preceding the development of the majority subset of B cells. d. They have little or no IgD on the cell surface. e. All of the above.

e. All of the above.

Which of the following would occur after the production of a functional μ chain as a pre-B-cell receptor? a. RAG proteins are degraded. b. The chromatin structure of the heavy-chain locus is reorganized to prevent gene rearrangement. c. Transcription of the RAG1 and RAG2 genes ceases. d. There is allelic exclusion of a second μ chain. e. All of the above.

e. All of the above.

All of the following statements regarding \gamma:\delta T cells are correct except a. thy are more abundant in tissue than in circulation b. the \delta chain is the counterpart to the \beta chain in \alpha:\beta T-cell receptors because it contsin V, D, and J segments in the variable region c. they share some properties with NK cells d. activation is not always dependent on recognition of peptide:MHC molecule complex e. expression on the cell surface is not dependent on the CD3 complex

e. expression on the cell surface is not dependent on the CD3 complex either e or b

Which of the following is not paired with its correct complement? a. N nucleotides : more abundant in rearranged heavy-chain genes that in rearranged light chain genes b. second checkpoint in B-cell development : assembly of a function B-cell receptor c. receptor editing : exchange of light chain for one that is not self-reactive d. first checkpoint in B-cell development : selection by the pre-B-cell receptor e. large pre-B-cell stage : constitutive expression of RAG-1 and RAG-2 proteins

e. large pre-B-cell stage : constitutive expression of RAG-1 and RAG-2 proteins

In which location would plasma cells not be present? a. bone marrow b. afferent lymphatic vessels c. medullary cords of lymph d. lamina propria of gut-associated lymphoid tissues e. red pulp of spleen f. efferent lymphatic vessels

e. red pulp of spleen

Which of the following cell types does not express MHC class I?

erythrocyte

CD8 T-cell subpopulations are specialized to combat _______ pathogens, whereas CD4 T-cell subpopulations are specialized to combat _______ pathogens.

intracellular extracellular

Large pre-B cells are characterized by __________.

nonproductive rearrangement of both heavy-chain loci has already occured

Describe a ligand for an α:β T-cell receptors.

peptide:MHC complex

? Cross-priming of the immune response occurs when _________.

phagolysosome-derived peptides bind to MHC class II molecules

Cross-priming of the immune response occurs when _________.

phagolysosome-derived peptides bind to MHC class II molecules

Describe the sequence of events involved in processing of peptides that will be presented as antigens with MHC class I.

proteasome → TAP1/2 → endoplasmic reticulum → MHC class I → plasma membrane

In contrast to immunoglobulin, \alpha:\beta T-cell receptors recognize epitopes present on ___________ antigens.

protein

Immature B cells develop into B cells in the _________.

secondary lymphoid organs

The CDR3 loops of the T-cell receptors contact the ___________.

side chains of amino acids in the middle of the peptide

skip

skip

When producing monoclonal antibodies, why is it important to use a fusion partner to myeloma cell that is unable to produce its own immunoglobulin?

to ensure that the antibodies are homogeneous and able to make strong bivalent attachments to multivalent antigens

The role of the CD3 proteins and ζ chain on the surface of the cell is to:

transduce signals to the interior of the T cell.

T-cell receptors intact not only with peptide anchored in the peptide-binding groove of MHC molecule,s but also with _______.

variable amino acid residues on α helices of the MHC molecule

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, the the δ-chain locus is _________.

α deleted

The CDR1 and CDR2 loops of the T-cell receptor contact the ______________.

α helices of the MHC molecules

The peptide-binding groove of MHC class I molecule is composed of what extracellular domains?

α1 : α2

To which domain of MHC class I does CD8 bind?

α3

To which domain of MHC class II does CD4 bind?

β2

The ___ light-chain genes rearrange before the ____ genes.

κ λ

In terms of V, D, and J segment arrangement, the T-cell receptor α-chain locus resembles the immunoglobulin _______ locus, whereas the T-cell receptor β-chain locus resembles the immunoglobulin _______ locus.

κ light chain