Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 5, Pages 1927-1932Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1500943
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Funding
- National Institute of Allergy and Infectious Diseases [AI049313, AR048632, AI111224]
- Bill and Melinda Gates Foundation Vaccine Accelerator Award
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The now-famous term restriction derived from experiments in which T cells from Donor A failed to recognize Ags presented by cells from Donor B. Restriction results from interdonor variation in MHC genes. Donor restriction dominates immunologists' 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 donor unrestricted 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, mucosaassociated 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.
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