MHC complex and antigen presentation MCQs With Answer

MHC complex and antigen presentation MCQs With Answer is a focused quiz set designed for M.Pharm students studying Immunotechnology. This collection reviews fundamental and advanced concepts of antigen processing and presentation, MHC structure and polymorphism, intracellular peptide-loading pathways, and clinical implications such as transplantation and drug hypersensitivity. Questions emphasize mechanistic details—proteasome/immunoproteasome roles, TAP transport, invariant chain/CLIP/HLA-DM function, cross-presentation, and non-classical antigen presentation—plus laboratory techniques used to study peptide–MHC interactions. Each MCQ includes concise options and the correct answer to help reinforce learning, prepare for exams, and support deeper understanding required for pharmaceutical research and immunotherapeutic development.

Q1. Which intracellular pathway is primarily responsible for generating peptides that are loaded onto MHC class I molecules?

• Cytosolic proteasomal degradation with peptide transport into the ER by TAP
• Endosomal/lysosomal proteolysis followed by loading in MIIC compartments
• Golgi apparatus sorting and direct loading onto MHC I in the trans-Golgi
• Secretory pathway cleavage by signal peptidase and loading in secretory vesicles

Correct Answer: Cytosolic proteasomal degradation with peptide transport into the ER by TAP

Q2. What is the typical length range of peptides bound by classical MHC class II molecules?

• 8–10 amino acids
• 13–25 amino acids
• 30–50 amino acids
• 3–6 amino acids

Correct Answer: 13–25 amino acids

Q3. What is the primary function of HLA-DM in the MHC class II antigen presentation pathway?

• Transport peptides from cytosol into the ER for MHC II loading
• Catalyze release of CLIP and facilitate peptide exchange on MHC II
• Trim N-terminal residues of peptides in the cytosol
• Form the peptide-binding groove of MHC II molecules

Correct Answer: Catalyze release of CLIP and facilitate peptide exchange on MHC II

Q4. Which statement best describes the role of the invariant chain (Ii) in MHC class II biosynthesis?

• It acts as a TAP substitute to transport peptides into the ER
• It blocks the peptide-binding groove in the ER and targets MHC II to endosomal compartments
• It trims peptides to appropriate length for MHC II binding
• It anchors MHC II to the plasma membrane after peptide loading

Correct Answer: It blocks the peptide-binding groove in the ER and targets MHC II to endosomal compartments

Q5. A defect in TAP proteins most directly leads to which of the following outcomes?

• Increased surface expression of MHC class II molecules
• Decreased surface expression of MHC class I molecules
• Enhanced cross-presentation of exogenous antigens
• Loss of invariant chain function

Correct Answer: Decreased surface expression of MHC class I molecules

Q6. What is the phenomenon of cross-presentation?

• Presentation of endogenous peptides on MHC class II molecules
• Presentation of exogenous antigens on MHC class I molecules by certain APCs
• Transfer of MHC-peptide complexes between cells through trogocytosis
• Presentation of lipid antigens by classical MHC molecules

Correct Answer: Presentation of exogenous antigens on MHC class I molecules by certain APCs

Q7. Where is the highest degree of polymorphism found in MHC molecules and why is it functionally important?

• Transmembrane region; it determines membrane anchoring strength
• Peptide-binding groove; it alters peptide-binding specificity and antigen repertoire
• Signal peptide; it changes ER targeting efficiency
• Beta-2 microglobulin; it controls association with CD8

Correct Answer: Peptide-binding groove; it alters peptide-binding specificity and antigen repertoire

Q8. CD1 molecules are specialized to present which type of antigens and to which T cell subset are they most commonly presented?

• Peptide antigens to conventional CD8+ T cells
• Lipid and glycolipid antigens to NKT cells
• Nucleic acid antigens to B cells
• Carbohydrate antigens to regulatory T cells

Correct Answer: Lipid and glycolipid antigens to NKT cells

Q9. How do bacterial superantigens activate large numbers of T cells?

• By being processed into peptides that tightly bind MHC I
• By cross-linking conserved regions of TCR Vβ with MHC class II outside the peptide groove
• By directly phosphorylating TCR signaling proteins
• By inhibiting HLA-DM and causing accumulation of CLIP

Correct Answer: By cross-linking conserved regions of TCR Vβ with MHC class II outside the peptide groove

Q10. Which HLA allele is strongly associated with abacavir hypersensitivity and is therefore tested clinically before therapy?

• HLA-B*08:01
• HLA-B*57:01
• HLA-DRB1*15:01
• HLA-A*02:01

Correct Answer: HLA-B*57:01

Q11. The immunoproteasome differs from the constitutive proteasome in that it:

• Is located only in the nucleus and does not generate antigenic peptides
• Contains inducible catalytic subunits that alter cleavage specificity to favor MHC I peptide generation
• Transports peptides into the ER independently of TAP
• Directly loads peptides onto MHC II molecules

Correct Answer: Contains inducible catalytic subunits that alter cleavage specificity to favor MHC I peptide generation

Q12. Which laboratory method provides the highest resolution for HLA typing used in transplantation and immunogenetics?

• Serological typing by complement-dependent cytotoxicity
• PCR-SSP (sequence-specific primers) low-resolution typing
• Sequence-based typing (SBT) / next-generation sequencing for high-resolution allelic identification
• Flow cytometry using anti-HLA monoclonal antibodies

Correct Answer: Sequence-based typing (SBT) / next-generation sequencing for high-resolution allelic identification

Q13. ERAAP (ER aminopeptidase associated with antigen processing) performs which enzymatic function relevant to MHC class I presentation?

• Ubiquitinates proteins to target them to the proteasome
• Trims N-terminal residues from peptides in the ER to optimize length for MHC I binding
• Removes CLIP from MHC II molecules in endosomes
• Glycosylates MHC class I heavy chain in the Golgi

Correct Answer: Trims N-terminal residues from peptides in the ER to optimize length for MHC I binding

Q14. What is the main application of peptide–MHC tetramers in immunological research?

• To quantify cytokine production by APCs
• To detect and enumerate antigen-specific T cells by flow cytometry
• To block T cell activation by competitive inhibition
• To sequence T cell receptor genes

Correct Answer: To detect and enumerate antigen-specific T cells by flow cytometry

Q15. The term ‘MHC restriction’ refers to which of the following principles?

• T cells recognize antigenic peptides only when presented by the host’s own MHC molecules
• B cells require MHC molecules to secrete antibodies
• MHC molecules can present only self-peptides to avoid autoimmunity
• Only non-peptide antigens can be presented by MHC molecules

Correct Answer: T cells recognize antigenic peptides only when presented by the host’s own MHC molecules

Q16. Which genes are encoded in the HLA class III region and what is their general functional class?

• HLA class III encodes the classical MHC I alpha chains used for antigen presentation
• HLA class III encodes complement components and cytokines, involved in innate and inflammatory responses
• HLA class III encodes TAP and proteasome subunits exclusively
• HLA class III encodes invariant chain and HLA-DM proteins for MHC II loading

Correct Answer: HLA class III encodes complement components and cytokines, involved in innate and inflammatory responses

Q17. Which statement accurately describes the role of TAP in antigen presentation?

• TAP degrades proteins into peptides in the cytosol
• TAP transports peptides from the cytosol into the endoplasmic reticulum for MHC I loading
• TAP exchanges peptides on MHC II in late endosomes
• TAP glycosylates MHC I heavy chains in the ER

Correct Answer: TAP transports peptides from the cytosol into the endoplasmic reticulum for MHC I loading

Q18. Which cell types are considered professional antigen-presenting cells capable of efficient naive T cell priming?

• Neutrophils and eosinophils only
• Dendritic cells, macrophages and B cells
• All nucleated cells in the body
• Red blood cells and platelets

Correct Answer: Dendritic cells, macrophages and B cells

Q19. How does MHC polymorphism contribute to outcomes in organ transplantation?

• Polymorphism has no impact; only blood group matters
• Differences in MHC alleles between donor and recipient increase risk of graft rejection due to T cell recognition of non-self MHC
• MHC polymorphism only affects susceptibility to viral infections, not transplantation
• Greater polymorphism always improves graft acceptance

Correct Answer: Differences in MHC alleles between donor and recipient increase risk of graft rejection due to T cell recognition of non-self MHC

Q20. In the structure of MHC class II molecules, which domains form the peptide-binding groove?

• Alpha1 and alpha2 domains
• Beta2-microglobulin and alpha3 domains
• Alpha1 and beta1 domains
• Alpha3 and beta2 domains

Correct Answer: Alpha1 and beta1 domains

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