T-cell development: positive and negative selection !

Process

Young T cells are trained in the thymus: those that cannot see our MHC die, and those that attack our own tissues are removed.

Updated 2026-11-01

See it in 3D: Thymus

What it is

T-cell precursors leave the bone marrow and mature in the thymus. They build a T-cell receptor by gene rearrangement, then pass two tests: positive selection keeps cells that can bind self-MHC (MHC restriction), and negative selection removes cells that bind self-peptides too strongly (central tolerance). Only a small fraction survives and leaves as naive CD4 or CD8 T cells.

Key facts

Most thymocytes die during selection; only a few percent leave the thymus.
The thymus is largest relative to body size in childhood and is gradually replaced by fat after puberty.
B cells undergo a similar selection in the bone marrow.

Step by step

Lymphoid precursors from the bone marrow enter the thymus; they lack CD4 and CD8 (double-negative).
In the cortex, RAG enzymes rearrange the TCR beta chain, then the alpha chain.
Cells become double-positive (CD4+ CD8+).
Positive selection in the cortex: cortical epithelial cells present self-MHC; cells that cannot bind it die by neglect.
Binding class I leads to CD8 cells; binding class II leads to CD4 cells (single-positive).
Negative selection, mainly in the medulla: cells that bind self-peptide on MHC too strongly die by apoptosis.
AIRE in medullary epithelial cells makes them show proteins from other organs, such as insulin.
Some self-reactive CD4 cells become regulatory T cells (FOXP3); survivors leave as naive T cells.

Clinical notes

DiGeorge syndrome (22q11.2 deletion): absent or small thymus, low T cells, hypocalcemia from absent parathyroids and heart defects.
AIRE mutations: autoimmune polyendocrine syndrome type 1 (hypoparathyroidism, adrenal insufficiency, chronic mucocutaneous candidiasis).
RAG deficiency or ADA deficiency: severe combined immunodeficiency.
Thymoma is associated with myasthenia gravis.

Test yourself

Think of the answer, then tap the question to see it.

Where does positive selection take place, and what does it test?

In the thymic cortex; it keeps thymocytes whose TCR can bind self-MHC, which establishes MHC restriction.

What is the role of AIRE?

It makes medullary thymic epithelial cells express proteins of other tissues so that self-reactive T cells are deleted; its loss causes autoimmune polyendocrine syndrome type 1.

A double-positive thymocyte binds MHC class II. What does it become?

A single-positive CD4 T cell.

Which syndrome combines thymic aplasia, hypocalcemia and heart defects?

DiGeorge syndrome, from a 22q11.2 deletion affecting third and fourth pharyngeal pouch development.

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See it in 3D

The structures of Durgical's 3D anatomy where it is found.

Thymus

Adenosine deaminase deficiency (ADA-SCID)

← All of immunology

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: 18.3 T Lymphocytes and Cellular Immunity (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.