🧠 MHC I vs MHC II for USMLE Step 1: Antigen Presentation, T-Cell Types, and Diseases

Understanding MHC class I and class II molecules is key for crushing Step 1 immunology questions. Whether it’s T-cell activation, HLA associations, or immunodeficiencies, you’ll be tested on these pathways repeatedly.

Let’s break down the structure, source of antigens, presentation to T cells, and high-yield diseases linked to each — with KOTC visuals and mnemonics to seal it in.

🧬 Quick Comparison Chart

Feature	MHC I	MHC II
Found On	All nucleated cells	APCs (dendritic cells, macrophages, B cells)
Presents To	CD8⁺ T cells	CD4⁺ T cells
Antigen Source	Endogenous (viral/intracellular)	Exogenous (bacterial/extracellular)
Processing Location	Cytosol → ER	Endosome → lysosome
Key Molecule	β2-microglobulin	Invariant chain
HLA Subtypes	A, B, C	DR, DP, DQ

🔄 Processing Pathways in Detail

🧬 MHC I Pathway (Endogenous)

1. Intracellular proteins (e.g., viral) degraded by proteasome

2. Peptides transported into ER via TAP proteins

3. Loaded onto MHC I, shipped to surface

4. Presented to CD8⁺ T cells → kill infected cells

🦠 MHC II Pathway (Exogenous)

1. Phagocytosed proteins degraded in lysosome

2. MHC II initially bound to invariant chain

3. Invariant chain removed, antigen loaded in vesicle

4. Presented to CD4⁺ T cells → coordinate immune response

🩺 High-Yield Clinical Correlations

Topic	MHC Class Involved
Viral infections	MHC I + CD8⁺
Bacterial toxins	MHC II + CD4⁺
Autoimmune diseases (e.g., Type 1 Diabetes, RA, Celiac)	MHC II HLA subtypes (DR, DQ)
Organ rejection (cytotoxic T cell–mediated)	MHC I mismatch
Bare Lymphocyte Syndrome	MHC I or II deficiency, depending on gene affected

🧠 Remember:

• CD8 = 1×8 = MHC I

• CD4 = 2×2 = MHC II

🧠 Mnemonics to Master It

“Infected cells use MHC I for Intracellular viruses”

“2 + 2 = 4 → CD4 + MHC II = Helper response”

🧬 HLA Subtypes for Step 1 (Partial List)

HLA Type	Associated Diseases
HLA-B27	Psoriasis, Ankylosing Spondylitis, IBD, Reactive Arthritis ("PAIR")
HLA-DR3	Type 1 Diabetes, Graves Disease, SLE
HLA-DR4	Rheumatoid Arthritis, Type 1 Diabetes
HLA-DQ2/DQ8	Celiac Disease ("I 8 2 much gluten")

🎯 Call-To-Action

Ready to ace all things immuno?

🧠 Drill MHC pathways and HLA associations in KOTC’s daily question sets and image library:
🔗 https://kingofthecurve.org/trial-sessions

📲 Or go lifetime access for instant mastery over every immune map, chart, and quiz:
🔗 https://kingofthecurve.org/free-lifetime

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Frequently Asked Questions (FAQs)

• How many hours should I study for the MCAT each day?

  Aim for 4-6 focused hours, ensuring you incorporate breaks to avoid burnout.

• What is the best way to handle test anxiety?

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• How can I stay motivated during the long application process?

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