Immunology · Adaptive immunity
MHC/HLA class I and II !
- Molecule
Display molecules on our cells that show protein fragments to T cells; in humans they are called HLA and differ from person to person.
Updated 2026-11-01
What it is
The major histocompatibility complex (MHC), called HLA in humans and encoded on chromosome 6, makes surface molecules that hold peptides for T cells to inspect. Class I (HLA-A, -B, -C) is on almost all nucleated cells and shows intracellular peptides to CD8 T cells; class II (HLA-DP, -DQ, -DR) is on antigen-presenting cells and shows extracellular peptides to CD4 T cells. HLA genes are highly polymorphic, which matters for transplant matching and for disease associations.
Key facts
- HLA genes are inherited as haplotypes, one from each parent; a sibling has a one-in-four chance of being HLA-identical.
- NK cells kill cells that lose class I, a common viral and tumor escape strategy.
- Interferon-gamma increases expression of both MHC classes.
MHC class I versus class II
| Feature | Class I | Class II |
|---|---|---|
| Genes | HLA-A, HLA-B, HLA-C | HLA-DP, HLA-DQ, HLA-DR |
| Where it is expressed | All nucleated cells and platelets (not mature red cells) | Professional antigen-presenting cells: dendritic cells, macrophages, B cells |
| Structure | One alpha chain with three domains plus beta-2 microglobulin | Alpha and beta chains, both crossing the membrane |
| Peptide source | Intracellular (cytosolic) proteins, for example viral | Extracellular proteins taken up into endosomes |
| Loading | Proteasome, TAP, endoplasmic reticulum | Endosome; invariant chain and CLIP exchanged with help from HLA-DM |
| T cell that reads it | CD8 cytotoxic T cell | CD4 helper T cell |
Clinical notes
- HLA-B27: ankylosing spondylitis, reactive arthritis, psoriatic arthritis and arthritis of inflammatory bowel disease.
- HLA-DR3 and HLA-DR4: type 1 diabetes.
- HLA-DQ2 and HLA-DQ8: celiac disease.
- HLA-DR4 (shared epitope): rheumatoid arthritis.
- HLA-B*57:01: hypersensitivity to abacavir, so it is tested before that drug is used.
- Bare lymphocyte syndrome (MHC class II deficiency): very few CD4 T cells and combined immunodeficiency.
Test yourself
Think of the answer, then tap the question to see it.
Which T cell recognizes peptides presented on MHC class I?
The CD8 cytotoxic T cell.
Which cells normally express MHC class II?
Professional antigen-presenting cells: dendritic cells, macrophages and B cells (thymic epithelium also expresses it).
Which HLA allele is associated with ankylosing spondylitis?
HLA-B27.
Which protein forms the light chain of MHC class I?
Beta-2 microglobulin.
Which HLA molecules are associated with celiac disease?
HLA-DQ2 and HLA-DQ8.
Related
- Antigen processing and presentation
- T-cell development: positive and negative selection
- T-cell activation: two signals and superantigens
- HLA associations with disease
- Transplant rejection: hyperacute, acute, chronic
- CD4⁺ helper T cell
- CD8⁺ cytotoxic T cell
- Natural killer cell
Related conditions
Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.
Sources: 18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells (OpenStax (Microbiology), 2016); 21.3 The Adaptive Immune Response: T lymphocytes and Their Functional Types (OpenStax (Anatomy and Physiology 2e), 2022).
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Representative model, for educational purposes only.