[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Adaptive immunity](https://durgical.com/en/immunology/#a-adaptive) › T-cell development: positive and negative selection [Immunology](https://durgical.com/en/immunology/) · [Adaptive immunity](https://durgical.com/en/immunology/#a-adaptive) # 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](https://durgical.com/en/anatomy/thymus/) ## Key points - Positive selection (cortex): binds self-MHC, gives MHC restriction. - Negative selection (medulla): strong binding to self-peptide, cell dies; central tolerance. - AIRE lets medullary cells display tissue-specific proteins; its loss causes APS-1. - Double-negative, then double-positive, then single-positive (CD4 or CD8). - DiGeorge: thymic aplasia, hypocalcemia, conotruncal heart defects. ## 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. ## Memory aid In the thymus, the cortex asks «can you see?» (positive) and the medulla asks «are you dangerous?» (negative). Fail the first and you are ignored; fail the second and you are removed. ## 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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/immunology/t-cell-development-positive-and-negative-selection/) ## See it in 3D The structures of Durgical's 3D anatomy where it is found. - [Thymus](https://durgical.com/en/anatomy/thymus/) ## Related - [MHC/HLA class I and II](https://durgical.com/en/immunology/mhc-hla-class-i-and-ii/) - [T-cell activation: two signals and superantigens](https://durgical.com/en/immunology/t-cell-activation-two-signals-and-superantigens/) - [Adaptive immunity (overview: humoral vs cellular)](https://durgical.com/en/immunology/adaptive-immunity/) - [Thymus: where T cells learn](https://durgical.com/en/immunology/thymus-where-t-cells-learn/) - [Immune tolerance and how autoimmunity begins](https://durgical.com/en/immunology/immune-tolerance-and-how-autoimmunity-begins/) - [Regulatory T cell (Treg, FOXP3)](https://durgical.com/en/immunology/regulatory-t-cell/) - [T-cell and combined deficiencies: DiGeorge, SCID, Wiskott–Aldrich, ataxia-telangiectasia](https://durgical.com/en/immunology/t-cell-and-combined-deficiencies-digeorge-scid-wiskott-aldrich-ataxia-telangiect/) - [CD markers: the table to know](https://durgical.com/en/immunology/cd-markers-the-table-to-know/) ## Related conditions - [Adenosine deaminase deficiency (ADA-SCID)](https://durgical.com/en/conditions/adenosine-deaminase-deficiency/) [← All of immunology](https://durgical.com/en/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](https://openstax.org/books/microbiology/pages/18-3-t-lymphocytes-and-cellular-immunity) (OpenStax (Microbiology), 2016); [21.3 The Adaptive Immune Response: T lymphocytes and Their Functional Types](https://openstax.org/books/anatomy-and-physiology-2e/pages/21-3-the-adaptive-immune-response-t-lymphocytes-and-their-functional-types) (OpenStax (Anatomy and Physiology 2e), 2022). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/immunology/t-cell-development-positive-and-negative-selection/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/t-cell-development-positive-and-negative-selection/