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MHC MOLECULES NOTES AND MCQ


MHC MOLECULES 


1. INTRODUCTION


MHC (Major Histocompatibility Complex): A set of cell surface proteins essential for the adaptive immune system to recognize foreign molecules.
Function: Presents antigenic peptides to T cells, initiating immune responses.
Location: Found in all vertebrates; in humans, MHC is called HLA (Human Leukocyte Antigen).
HLA Full Form: Human Leukocyte Antigen


2. Types of MHC Molecules

MHC molecules are classified into two main classes and a third minor class:
A. Class I MHC (MHC-I)
Expression: On all nucleated cells (except RBCs)
Function: Presents endogenous antigens (from inside the cell, e.g., viral proteins) to CD8+ cytotoxic T cells
Structure:
Heavy α chain (3 domains: α1, α2, α3)
Light chain (β2-microglobulin)
Peptide-binding groove formed by α1 and α2
Peptide length: Typically 8–10 amino acids
Genes: HLA-A, HLA-B, HLA-C (highly polymorphic)

B. Class II MHC (MHC-II)


Expression: On antigen-presenting cells (APCs) like dendritic cells, macrophages, B cells
Function: Presents exogenous antigens (from outside the cell) to CD4+ helper T cells
Structure:
Two chains: α (α1, α2) and β (β1, β2)
Peptide-binding groove formed by α1 and β1
Peptide length: Typically 13–25 amino acids
Genes: HLA-DP, HLA-DQ, HLA-DR


C. Class III MHC (MHC-III)


Not directly involved in antigen presentation
Includes: Complement proteins (C2, C4, B) and cytokines like TNF
Function: Supports immune response

3. Structure of MHC Molecules
MHC-I: Single α chain + β2-microglobulin + peptide
MHC-II: α and β chains + peptide
Polymorphism: High variability in peptide-binding regions ensures recognition of diverse antigens.
Co-dominant expression: Both maternal and paternal alleles are expressed.

4. Antigen Processing and Presentation

A. Endogenous Pathway (MHC-I)

Pathogens (e.g., viruses) replicate inside host cell.
Proteins degraded by proteasomes into peptides.
Peptides transported to ER via TAP (Transporter associated with antigen processing)
Peptides loaded onto MHC-I.
MHC-I-peptide complex transported to cell surface.
Recognized by CD8+ T cells → cytotoxic response

B. Exogenous Pathway (MHC-II)

APCs engulf pathogens via phagocytosis or endocytosis.
Pathogen degraded in endosomes/lysosomes.
MHC-II synthesized in ER with invariant chain (Ii) blocking peptide binding.
In endosome, invariant chain degraded, leaving CLIP fragment.
HLA-DM exchanges CLIP with antigenic peptide.
MHC-II-peptide complex transported to surface.
Recognized by CD4+ T cells → helper response

5. MHC Polymorphism and Diversity

Polymorphism: Multiple alleles exist for each MHC gene.
Polygeny: Multiple MHC genes exist within one class.

Significance:

Broadens the range of antigens recognized.
Ensures survival against diverse pathogens.
Important in organ transplantation.
6. Role in Immune Response

MHC-I: Cytotoxic T lymphocyte activation → kills infected or abnormal cells.
MHC-II: Helper T cell activation → cytokine release → B cell activation → antibody production.
Self vs Non-self recognition: Prevents autoimmune response.

7. Clinical Significance
Transplantation: MHC mismatch → graft rejection
Autoimmune diseases: HLA-B27 → ankylosing spondylitis; HLA-DR3/DR4 → Type 1 diabetes
Disease susceptibility: Certain HLA alleles linked to infections.
Vaccine design: Understanding MHC-peptide binding enhances vaccine efficacy.

8. Key Points for Exams

MHC-I: All nucleated cells, endogenous antigens, CD8+ T cells.
MHC-II: APCs, exogenous antigens, CD4+ T cells.
MHC-III: Complement proteins and cytokines.
Polymorphism & Polygeny: Essential for immune diversity.
Antigen processing pathways: Endogenous → MHC-I, Exogenous → MHC-II.
Clinical relevance: Autoimmunity, transplantation, disease susceptibility.



MHC MOLECULES – 50 MCQs WITH ANSWERS


1–10: Basic Concepts


What does MHC stand for?
a) Major Histology Complex
b) Major Histocompatibility Complex
c) Multiple Histology Components
d) Minor Histocompatibility Complex
Answer: b


Human MHC is called:
a) HLA
b) HLB
c) HLC
d) HMC
Answer: a
MHC-I molecules present antigens to:
a) B cells
b) CD4+ T cells
c) CD8+ T cells
d) NK cells
Answer: c
MHC-II molecules present antigens to:
a) CD8+ T cells
b) CD4+ T cells
c) B cells only
d) Macrophages
Answer: b
MHC molecules are located on:
a) Only red blood cells
b) Only nucleated cells (Class I)
c) Only APCs (Class II)
d) Both B and C
Answer: d
Which MHC class includes complement proteins?
a) Class I
b) Class II
c) Class III
d) None
Answer: c
The peptide-binding groove of MHC-I is formed by:
a) α1 and α2
b) α2 and α3
c) β1 and β2
d) α1 and β1
Answer: a
The peptide-binding groove of MHC-II is formed by:
a) α1 and α2
b) α1 and β1
c) β1 and β2
d) α2 and β2
Answer: b
MHC molecules are highly:
a) Conserved
b) Polymorphic
c) Monomorphic
d) Homologous only to mice
Answer: b
Which MHC class is expressed on all nucleated cells?
a) Class I
b) Class II
c) Class III
d) None
Answer: a
11–20: Antigen Processing & Presentation
Endogenous antigens are presented via:
a) MHC-I
b) MHC-II
c) MHC-III
d) None
Answer: a
Exogenous antigens are presented via:
a) MHC-I
b) MHC-II
c) MHC-III
d) Both I & II
Answer: b
Proteasomes degrade antigens for which MHC class?
a) Class I
b) Class II
c) Class III
d) Both I & II
Answer: a
TAP protein transports peptides to:
a) Golgi apparatus
b) ER
c) Lysosome
d) Cytoplasm
Answer: b
The invariant chain (Ii) prevents premature binding in:
a) MHC-I
b) MHC-II
c) MHC-III
d) Both I & II
Answer: b
CLIP fragment is associated with:
a) MHC-I
b) MHC-II
c) Class III
d) None
Answer: b
HLA-DM function is to:
a) Degrade antigens
b) Transport peptides to ER
c) Exchange CLIP with antigenic peptide
d) Stimulate NK cells
Answer: c
MHC-I presents peptides of length:
a) 8–10 amino acids
b) 13–25 amino acids
c) 5–7 amino acids
d) 15–30 amino acids
Answer: a
MHC-II presents peptides of length:
a) 8–10 amino acids
b) 13–25 amino acids
c) 5–7 amino acids
d) 20–30 amino acids
Answer: b
APCs include:
a) Macrophages
b) Dendritic cells
c) B cells
d) All of the above
Answer: d
21–30: Genetics & Expression
HLA-A, HLA-B, and HLA-C belong to:
a) MHC-I
b) MHC-II
c) MHC-III
d) None
Answer: a
HLA-DP, DQ, DR belong to:
a) MHC-I
b) MHC-II
c) MHC-III
d) None
Answer: b
MHC genes are located on:
a) Chromosome 6
b) Chromosome 12
c) Chromosome 15
d) Chromosome X
Answer: a
Both maternal and paternal alleles are expressed – called:
a) Monogenic expression
b) Codominant expression
c) Recessive expression
d) Dominant expression
Answer: b
Polymorphism refers to:
a) Multiple cells expressing MHC
b) Multiple alleles of MHC genes
c) Single allele expression
d) Absence of diversity
Answer: b
Polygeny refers to:
a) Multiple MHC genes per class
b) Multiple antigens
c) Only one gene per class
d) None
Answer: a
The peptide-binding region is highly:
a) Conserved
b) Polymorphic
c) Monomorphic
d) Non-functional
Answer: b
MHC class I is involved in:
a) Helper T cell activation
b) Cytotoxic T cell activation
c) Complement activation
d) Antibody production
Answer: b
MHC class II is involved in:
a) Helper T cell activation
b) Cytotoxic T cell activation
c) Complement activation
d) None
Answer: a
Which statement is true?
a) RBCs express MHC-I
b) APCs express MHC-II
c) MHC-III directly presents antigens
d) None
Answer: b
31–40: Clinical Significance
HLA-B27 is associated with:
a) Type 1 Diabetes
b) Ankylosing Spondylitis
c) SLE
d) Rheumatoid Arthritis
Answer: b
HLA-DR3 and DR4 are linked to:
a) Multiple sclerosis
b) Type 1 Diabetes
c) Asthma
d) Psoriasis
Answer: b
MHC mismatch can lead to:
a) Autoimmunity
b) Graft rejection
c) Tolerance
d) None
Answer: b
Which MHC class has complement proteins?
a) I
b) II
c) III
d) None
Answer: c
Vaccines target MHC to:
a) Enhance peptide presentation
b) Destroy T cells
c) Suppress immune response
d) None
Answer: a
Autoimmune disease occurs due to:
a) MHC polymorphism
b) MHC mismatch recognition of self
c) Complement deficiency
d) B cell absence
Answer: b
Codominance of MHC ensures:
a) Only paternal alleles expressed
b) Only maternal alleles expressed
c) Both alleles expressed → broader immune recognition
d) No allele expressed
Answer: c
MHC is essential for:
a) Innate immunity only
b) Adaptive immunity
c) Physical barriers
d) Hormonal regulation
Answer: b
Peptide loading onto MHC-II occurs in:
a) ER
b) Endosome/lysosome
c) Cytoplasm
d) Golgi
Answer: b
TAP proteins are associated with:
a) MHC-I
b) MHC-II
c) Both
d) MHC-III
Answer: a
41–50: Advanced/Tricky
Beta-2 microglobulin is part of:
a) MHC-I
b) MHC-II
c) MHC-III
d) None
Answer: a
Helper T cells recognize:
a) MHC-I-peptide
b) MHC-II-peptide
c) Free antigens
d) Complement proteins
Answer: b
Cytotoxic T cells recognize:
a) MHC-I-peptide
b) MHC-II-peptide
c) Free antigens
d) B cell receptor
Answer: a
The invariant chain is degraded into:
a) TAP
b) CLIP
c) β2-microglobulin
d) Proteasome
Answer: b
Endogenous pathway antigens come from:
a) Extracellular bacteria
b) Intracellular viruses
c) Vaccines only
d) Complement proteins
Answer: b
Exogenous pathway antigens come from:
a) Intracellular viruses
b) Extracellular microbes
c) NK cells
d) RBCs
Answer: b
MHC molecules are involved in:
a) Self vs non-self discrimination
b) Blood clotting
c) Hormone secretion
d) Neural transmission
Answer: a
MHC-I peptide-binding groove is:
a) Open-ended
b) Closed-ended
c) Non-functional
d) Only for lipids
Answer: b
MHC-II peptide-binding groove is:
a) Closed-ended
b) Open-ended
c) Non-functional
d) Only for lipids
Answer: b
Highly polymorphic regions of MHC are located at:
a) Peptide-binding regions
b) Cytoplasmic tail
c) Transmembrane region
d) None
Answer: a

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