Tema 8 Flashcards
1. A hapten is best defined as being:
A An epitope
B A paratope
C A small chemical grouping that reacts with preformed antibodies
D A carrier
E An immunogen
No induce la formación de Ab pero puede reaccionar con ellos
2. A discontinuous antigen epitope is:
A Presented by MHC molecules
B Usually concave
C Representative of only a minority of B-cell epitopes
D Produced by a continuous linear peptide sequence
E Produced by amino acid residues on non-adjacent polypeptide sequences
E
3. Binding of antigen to antibody:
A Is usually unaffected by molecular rigidity
B Is unaffected by the presence or absence of water molecules
C Involves covalent bonding
D Is optimized by spatial complementarity
E Is usually unaffected by pH
D
4. The intermolecular forces that contribute to the interaction between antibody and antigen:
A Are all electrostatic
B Are all van der Waals
C Are all hydrophobic
D Are all hydrogen bonds
E Rely on a combination of the above
E
5. Which of the following statements is NOT TRUE of affinity?
A A measure of the strength of the binding of antigen to antibody
B The equilibrium constant of the Ag/Ab complex
C Avidity
D Related to the free energy change of the Ag/Ab interaction
E Related to specificity
C
E es vd pq + específico se entiende que la afinidad es mayor.
6. What is the structure recognized by the αβ T-cell receptor on the cell surface of an antigen-presenting cell?
A Native protein antigen plus major histocompatibility complex (MHC) molecule
B Processed (peptide) antigen plus MHC
C Processed peptide antigen
D Native antigen
E MHC alone
B
A y D–> no, pq eso sería lo que reconoce Bcell
7. The processing of cytosolic protein involves:
A Transport into late endosomes
B Proteasome-mediated cleavage
C Displacement of invariant chain
D Displacement of β2-microglobulin
E Binding to the MHC class II groove
B
Entendiendo prot citosólica como antígeno endógeno
The cytosolic proteins are cleaved to small peptides in the (immuno)proteasome complex before they are transported by the TAP-1/2 molecules into the endoplasmic reticulum. Exogenously derived proteins are processed within endocytic vesicles and become acidic late endosomes before fusion with MHC class II derived from the endoplasmic reticulum. Fusion with late endosomes leads to DM-catalyzed displacement of the invariant chain CLIP from its union with the nascent MHC class II molecules. Thereafter, appropriate peptides within the fused vacuoles combine with the MHC class II groove. The processed cytosolic proteins give rise to peptides which reinforce the stability of the β2-microglobulin–class I heavy chain complex. The cytosolic protein after processing binds to the MHC class I groove within the endoplasmic reticulum before transport to the surface.
8. Which of the following statements does NOT apply to the immunoproteasome?
A It is generated in response to IFNγ stimulation
B It contains the β-1i subunit
C It contains the β-5i subunit
D Very few of the peptides generated are 8–10 residues in length
E It contains a 19s regulator
D
Muy subjetivo según como se interprete generar (no se sintetiza de nuevo, se activa.
Well done, you have selected the right answer.
The correct answer is D. The immunoproteasome is specialized to produce a greater proportion of peptides of this length which is optimal for insertion into the MHC class I groove. IFNγ increases production of immunoproteasome-associated catalytic subunits which replace homologous catalytic subunits in the housekeeping proteasome. β-1i and β-5i replace the β1 subunit of the housekeeping proteasome during the generation of the immunoproteasome. Both the housekeeping proteasome and the immunoproteasome contain a 19s regulator to which proteins bind following their ubiquitination.
9. Antigen processing for presentation by MHC class II molecules involves:
A DM
B ERp57
C TAP1 and TAP2
D Calnexin
E Proteasomal-mediated cleavage
The correct answer is A. The MHC-related dimeric molecule DM catalyzes the removal of CLIP from the MHC class II binding groove and keeps the groove open so that peptides generated in the endosome can be incorporated. ERp57 isomerizes MHC class I disulfide bonds to ensure the correct conformation of MHC in the endoplasmic reticulum. The TAP1 and TAP2 transporters are employed in the translocation of peptides from the cytosol into the endoplasmic reticulum prior to the incorporation of the peptides into MHC class I molecules. Calnexin acts as a molecular chaperone for the MHC class I heavy chain prior to its assocation with β2 microglobulin together with peptide derived from endogenous antigen. Cleavage of proteins by the proteasome, and especially the immunoproteasome, provides a source of peptides for presentation by MHC class I.
10. The processed peptide binding to the MHC class I groove:
A Is usually more than 11 amino acids long
B Hangs over the ends of the groove
C Usually binds to the groove through two anchor residues
D Is mainly recognized by the CDR2 of the T-cell receptor chains
E Is mostly derived from exogenous protein taken in by endocytosis
C
A –> 9-10 aa
The correct answer is C. Each polymorphic MHC class I molecule usually has two, although sometimes there are three, major pockets associated with the groove which bind strongly to side chains on the processed peptide. The processed peptide fitting to the class I groove is usually 8–10 amino acids long. The peptide sits within the MHC class I groove and if it is slightly long, it kinks up in the middle. The CDR2 is mainly concerned in recognition of the MHC α helices. Peptide is recognized mainly by the CDR3 regions. CDR1 makes contacts with the MHC α helices, as well as some contacts with the peptide. The exogenous proteins are degraded and usually finish up in the MHC class II groove. Processed cytosolic proteins are usually bound finally to the MHC class I groove. Note, however, that “cross-presentation” also occurs at a significant rate.
11. TCR recognition of peptide-MHC class II depends on:
A Covalent binding
B Very high affinity interactions
C CDR-mediated binding
D A minimum of two peptides occupying the binding groove of each MHC molecule
E The presence of β2 microglobulin
The correct answer is C. As with antibody molecules, it is the CDRs that are primarily involved in the recognition process. Binding of the TCR to the peptide-MHC, like binding of antibody to antigen, is reversible and based upon non-covalent interactions. The interaction is of fairly low affinity with a Ka of around 104−107 M−1. Sufficiently high affinity to enable activation of the T-cell arises primarily because of the multiple interactions occurring which also involve various adhesion molecule pairs such as LFA-1–ICAM-1 and CD2–LFA-3. Only one peptide at a time can occupy the groove of a single MHC molecule as there is simply not enough room to accommodate more than one. β2 microglobulin is mandatory for cell surface expression of peptide-MHC class I, but is not a component of MHC class II.
12. Cross-presentation of exogenous antigen to αβ T-cells does NOT require the involvement of:
A Peptide-MHC recognition by the T-cell receptor
B Antigen-processing
C MHC class I
D MHC class II
E An antigen-presenting cell
D
D. Exogenous antigen is conventionally presented by MHC class II, but if being cross-presented on MHC class I then MHC class II is not required. All T-cells bearing an αβ T-cell receptor recognize peptide-MHC, irrespective of whether the antigen is exogenously or endogenously derived, conventionally presented or cross-presented. All T-cells bearing an αβ T-cell receptor recognize processed antigen presented by MHC molecules. Endogenous antigen is conventionally presented by MHC class I; therefore if exogenous antigen is being presented by class I this is referred to as cross-presentation. Some type of cell must by definition be cross-presenting the antigen. Dendritic cells, and to a lesser extent macrophages, are adept at cross-presenting exogenous antigen.
14. Which of the following statements is TRUE of CD1?
A CD1 is encoded in the MHC region
B CD1 structurally is most similar to MHC class II molecules
C CD1 can present antigens to γδ, but not αβ T-cells
D CD1 can present lipid antigens
E CD1 is encoded by a single gene
D
CD1 molecules are specialized for the presentation of lipid and glycolipid microbial antigens. CD1 is encoded on chromosome 1 in humans and chromosome 3 in mice, whereas the MHC genes are present on chromosomes 6 and 17 in human and mouse, respectively. Structurally, CD1 is most similar to MHC class I. Indeed, CD1 incorporates β2 microglobulin into its structure just like the classical MHC class I molecules. Clonally diverse γδ and αβ T-cell populations can recognize antigens presented by CD1. CD1 is a family of molecules (CD1a-e) each encoded by a separate gene.
16. Which of the following statements is TRUE of superantigens?
A Superantigens do not cause pathology
B Superantigens are not mitogenic for T-cells
C Superantigens bind to MHC class III
D Superantigens bind to all members of a given V β TCR family
E Superantigens have to be processed before recognition by the T-cell
D
Superantigens recognize the common structures in a given V β TCR family and bind to all of them, cross-linking the T-cell to the MHC class II on an antigen-presenting cell. This is a powerful stimulus. The pyogenic toxin superantigen family can cause food poisoning, fever, vomiting, and diarrhea. Superantigens are very powerfully mitogenic for T-cells bearing certain V β families and therefore cause their proliferation. Superantigens bind to MHC class II non-polymorphic sites. They combine with the V β TCR in their native state and do not require processing.
17. αβ T-cells recognizing MHC plus processed peptide can:
A Themselves produce antibody to directly eliminate extracellular organisms
B Release histamine
C Develop into γδ T-cells
D Directly kill viruses
E Recognize an intracellular infection
E
Los virus NO se matan directamente, matas la cél infectada
T-cells deal directly cell to cell with an infected cell, either through cytotoxicity or by release of appropriate cytokines such as the macrophage activating IFNγ. In order to recognize an intracellular infection, it uses the code, MHC = cell, processed peptide = infectious agent within the cell. Extracellular organisms are eliminated by antibody but this is produced by B-cells, although they usually require help from T-cells in order to do so. T-cells do not release histamine, this is a property of activated mast cells. αβ and γδ T-cells are two separate populations which do not convert into the other type. The T-cell does not recognize a virus directly. It sees peptide derived from intracellular virus associated with MHC and can kill the virally infected cell before the virus has had time to replicate significantly.
