Structure and role of Major Histocompatibility Complex (MHC) MCQs With Answer

Introduction: The Structure and role of Major Histocompatibility Complex (MHC) MCQs With Answer provides B. Pharm students a focused review of MHC architecture, antigen processing, and clinical relevance. Learn core keywords: MHC class I, MHC class II, HLA alleles, antigen presentation, proteasome, TAP, invariant chain, CLIP, antigen-presenting cells, polymorphism, transplant rejection, and drug hypersensitivity (e.g., abacavir). This concise guide explains molecular structure, peptide binding grooves, cellular pathways, and implications for vaccine design, immunogenicity, and pharmacovigilance. Clear MCQs emphasize mechanism and therapeutics to strengthen reasoning for pharmacy practice. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which components form the classical MHC class I molecule on the cell surface?

• A single transmembrane alpha chain associated non-covalently with beta2-microglobulin
• Two transmembrane chains (alpha and beta) with an invariant chain
• A heterodimer of alpha and beta chains identical to class II
• A soluble heavy chain secreted after peptide binding

Correct Answer: A single transmembrane alpha chain associated non-covalently with beta2-microglobulin

Q2. Typical peptides presented by MHC class I molecules are usually how many amino acids long?

• 8–10 amino acids
• 13–25 amino acids
• 30–50 amino acids
• No fixed length, always longer than 100 amino acids

Correct Answer: 8–10 amino acids

Q3. Which intracellular pathway primarily supplies peptides for MHC class I presentation?

• Endogenous proteasomal degradation of cytosolic proteins
• Endosomal/lysosomal degradation of extracellular proteins
• Secretory pathway cleavage in Golgi apparatus
• Mitochondrial proteases processing

Correct Answer: Endogenous proteasomal degradation of cytosolic proteins

Q4. TAP (Transporter associated with Antigen Processing) transports peptides into which cellular compartment?

• The endoplasmic reticulum lumen
• The Golgi cisternae
• The mitochondrial matrix
• The cytosol for proteasomal degradation

Correct Answer: The endoplasmic reticulum lumen

Q5. Which molecule stabilizes MHC class II alpha and beta chains in the ER and prevents premature peptide binding?

• Invariant chain (Ii)
• Beta2-microglobulin
• TAP
• Proteasome

Correct Answer: Invariant chain (Ii)

Q6. CLIP is best described as:

• A fragment of invariant chain that occupies the MHC II peptide-binding groove
• A proteasomal subunit generating class I peptides
• A transporter that moves peptides into the ER
• An MHC class I-associated chaperone analogous to beta2-microglobulin

Correct Answer: A fragment of invariant chain that occupies the MHC II peptide-binding groove

Q7. HLA-DM functions primarily to:

• Facilitate removal of CLIP and promote peptide loading onto MHC II
• Transport peptides into the ER for MHC I loading
• Stabilize MHC I heavy chain before beta2-microglobulin binding
• Degrade endogenous proteins into peptides

Correct Answer: Facilitate removal of CLIP and promote peptide loading onto MHC II

Q8. Which cells constitutively express high levels of MHC class II molecules?

• Dendritic cells, macrophages, and B lymphocytes
• All nucleated cells including neurons
• Red blood cells and platelets
• Hepatocytes exclusively

Correct Answer: Dendritic cells, macrophages, and B lymphocytes

Q9. CD8+ T cells recognize antigenic peptides presented by which MHC class?

• MHC class I
• MHC class II
• Non-classical MHC class III
• Secreted MHC-like molecules in plasma

Correct Answer: MHC class I

Q10. MHC restriction refers to:

• The requirement that T cells recognize antigenic peptide bound to self-MHC molecules
• The limitation of MHC expression to lymphoid tissues only
• The exclusive presentation of bacterial peptides by MHC II
• The inability of MHC to bind peptides from mutated proteins

Correct Answer: The requirement that T cells recognize antigenic peptide bound to self-MHC molecules

Q11. High polymorphism in HLA genes is important because it:

• Increases population-level ability to present diverse peptides and resist pathogens
• Prevents any individual from presenting peptides at all
• Limits antigen presentation to viral peptides only
• Causes uniform transplant compatibility worldwide

Correct Answer: Increases population-level ability to present diverse peptides and resist pathogens

Q12. Abacavir hypersensitivity is associated with which HLA allele, illustrating MHC relevance in drug reactions?

• HLA-B*57:01
• HLA-DR4
• HLA-A*02:01
• HLA-DQ2

Correct Answer: HLA-B*57:01

Q13. Cross-presentation allows exogenous antigens to be presented on:

• MHC class I molecules to activate CD8+ T cells
• MHC class II molecules exclusively on epithelial cells
• MHC class III molecules to activate B cells
• Secreted MHC molecules to neutralize toxins

Correct Answer: MHC class I molecules to activate CD8+ T cells

Q14. Non-classical MHC molecules (e.g., HLA-E, HLA-G) primarily function to:

• Modulate innate and adaptive immune interactions, including NK cell recognition
• Replace beta2-microglobulin in class I molecules
• Present long peptides to CD4+ T cells
• Transport peptides across membranes

Correct Answer: Modulate innate and adaptive immune interactions, including NK cell recognition

Q15. Which enzyme complex generates many peptides for MHC class I presentation?

• Proteasome (including immunoproteasome variants)
• Lysosomal cathepsins only
• Ribosomal peptidyl transferase
• Golgi-associated signal peptidase

Correct Answer: Proteasome (including immunoproteasome variants)

Q16. A key difference between MHC class I and class II peptide-binding grooves is:

• Class I groove is closed at ends favoring shorter peptides; class II groove is open allowing longer peptides
• Class I groove binds only glycoproteins; class II binds lipids
• Class I groove is located in cytosol; class II groove is nuclear
• Class I groove requires invariant chain; class II does not

Correct Answer: Class I groove is closed at ends favoring shorter peptides; class II groove is open allowing longer peptides

Q17. In the context of transplantation, matching which loci reduces risk of graft rejection most significantly?

• HLA-A, HLA-B, and HLA-DR
• HLA-C only
• All mitochondrial DNA haplotypes
• HLA-DM and HLA-DO exclusively

Correct Answer: HLA-A, HLA-B, and HLA-DR

Q18. Which experimental technique is commonly used to type HLA alleles at high resolution?

• Sequence-based typing (DNA sequencing of HLA genes)
• Western blot of serum proteins
• Enzyme-linked immunosorbent assay (ELISA) for cytokines
• Standard Gram staining

Correct Answer: Sequence-based typing (DNA sequencing of HLA genes)

Q19. MHC class II molecules primarily present peptides derived from:

• Extracellular proteins internalized and processed in endosomes/lysosomes
• Proteins synthesized in the cytosol degraded by proteasome
• Inner mitochondrial proteins via TOM/TIM system
• Secreted hormones from endocrine glands

Correct Answer: Extracellular proteins internalized and processed in endosomes/lysosomes

Q20. A vaccine designed to elicit robust CD8+ T cell responses should ensure effective presentation on:

• MHC class I molecules (via intracellular antigen delivery or cross-presentation)
• MHC class II molecules only
• Secreted immunoglobulins
• Major urinary proteins

Correct Answer: MHC class I molecules (via intracellular antigen delivery or cross-presentation)

Q21. Which statement best describes HLA linkage disequilibrium?

• Certain HLA alleles at adjacent loci are inherited together more frequently than expected by chance
• All HLA loci assort independently in populations
• HLA alleles are evenly distributed without population differences
• Linkage disequilibrium prevents any HLA polymorphism

Correct Answer: Certain HLA alleles at adjacent loci are inherited together more frequently than expected by chance

Q22. Which chaperone complex assists folding and assembly of MHC class I heavy chain and beta2-microglobulin in the ER?

• Calnexin and calreticulin together with tapasin as part of the peptide-loading complex
• Invariant chain and HLA-DM complex
• Proteasome and TAP complex
• Lysosomal cathepsins and HLA-DR

Correct Answer: Calnexin and calreticulin together with tapasin as part of the peptide-loading complex

Q23. Which role of MHC polymorphism directly impacts peptide binding?

• Variation in amino acids in the peptide-binding groove alters specificity and anchor residue preference
• Polymorphism affects only the transmembrane region without changing binding
• Polymorphism solely determines cytokine secretion profile
• Polymorphism eliminates antigen presentation entirely

Correct Answer: Variation in amino acids in the peptide-binding groove alters specificity and anchor residue preference

Q24. Superantigens activate large numbers of T cells by binding to:

• Variable region of the TCR beta chain and MHC class II outside the peptide groove
• Peptide within MHC class I groove only
• Invariant chain to prevent peptide loading
• Beta2-microglobulin to stabilize MHC I

Correct Answer: Variable region of the TCR beta chain and MHC class II outside the peptide groove

Q25. Which clinical test uses knowledge of MHC compatibility directly before organ transplantation?

• Crossmatch and HLA typing
• Serum glucose measurement
• Liver function panel only
• Skin prick allergy test

Correct Answer: Crossmatch and HLA typing

Q26. Immunoproteasomes induced by IFN-γ alter peptide generation to:

• Produce peptides more suitable for MHC class I presentation during inflammation
• Inhibit peptide generation for class I completely
• Direct peptides exclusively into the lysosomal pathway
• Generate peptides only for MHC class II

Correct Answer: Produce peptides more suitable for MHC class I presentation during inflammation

Q27. Which of the following best explains why some autoimmune diseases are associated with particular HLA alleles?

• Certain HLA alleles present self-peptides that trigger autoreactive T cells more efficiently
• HLA alleles cause complete absence of immune cells
• HLA alleles are unrelated to autoimmunity
• HLA alleles prevent antigen processing entirely

Correct Answer: Certain HLA alleles present self-peptides that trigger autoreactive T cells more efficiently

Q28. In antigen processing for MHC class II, which proteases are mainly involved in peptide generation within endosomes?

• Cathepsins (e.g., cathepsin S, L)
• Proteasomal subunits beta1, beta2
• Ribonucleases in the nucleus
• Signal peptidase in the ER membrane

Correct Answer: Cathepsins (e.g., cathepsin S, L)

Q29. Which statement about beta2-microglobulin is correct?

• It is non-covalently associated with MHC class I heavy chain and required for surface expression
• It is an invariant chain fragment for MHC II
• It transports peptides into endosomes
• It is a proteasomal catalytic subunit

Correct Answer: It is non-covalently associated with MHC class I heavy chain and required for surface expression

Q30. For rational vaccine design, understanding MHC-peptide binding motifs helps to:

• Select epitopes that are widely presented across common HLA alleles to maximize population coverage
• Ensure vaccines avoid any peptide presentation by MHC
• Design vaccines that rely solely on innate immunity without T cell help
• Exclude any consideration of polymorphism or T cell epitopes

Correct Answer: Select epitopes that are widely presented across common HLA alleles to maximize population coverage

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com