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Donor restriction dominates immunologists\u2019 thinking about the T cell response because it governs organ transplantation and hinders the discovery of disease-associated Ags. However, other T cells can be considered \u201cdonor unrestricted\u201d because their targets, CD1a, CD1b, CD1c, CD1d, or MR1, are expressed in a similar form among all humans. A striking feature of donor unrestricted T cells is the expression of invariant TCRs with nearly species-wide distribution. In this article, we review new evidence that donor unrestricted T cells are common in humans. NKT cells, mucosa-associated invariant T cells, and germline-encoded mycolyl-reactive T cells operate outside of the familiar principles of the MHC system, providing a broader picture of T cell function and new opportunities for therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.1500943","type":"journal-article","created":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T20:49:06Z","timestamp":1440190146000},"page":"1927-1932","source":"Crossref","is-referenced-by-count":78,"title":["Donor Unrestricted T Cells: A Shared Human T Cell Response"],"prefix":"10.1093","volume":"195","author":[{"given":"Ildiko","family":"Van Rhijn","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"},{"name":"Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University , 3584CL Utrecht ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Branch","family":"Moody","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2025030704073153500_r1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/248701a0","article-title":"Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system","volume":"248","author":"Zinkernagel","year":"1974","journal-title":"Nature"},{"key":"2025030704073153500_r2","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1046\/j.1365-3083.1997.d01-149.x","article-title":"The Nobel Lectures in Immunology. 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