🧠 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)
Intracellular proteins (e.g., viral) degraded by proteasome
Peptides transported into ER via TAP proteins
Loaded onto MHC I, shipped to surface
Presented to CD8⁺ T cells → kill infected cells
🦠 MHC II Pathway (Exogenous)
Phagocytosed proteins degraded in lysosome
MHC II initially bound to invariant chain
Invariant chain removed, antigen loaded in vesicle
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
Frequently Asked Questions (FAQs)
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Aim for 4-6 focused hours, ensuring you incorporate breaks to avoid burnout.
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Practice mindfulness techniques, take practice exams under realistic conditions, and maintain a balanced lifestyle.
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Set short-term goals, seek support from mentors, and reward yourself for small achievements.
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Regular exercise improves focus, reduces stress, and enhances overall mental clarity.
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KOTC offers personalized learning tools, gamification features, and adaptive question banks to help students stay on track without burnout.
