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Rockefeller University Press, Journal of Experimental Medicine, 4(195), p. 485-494, 2002

DOI: 10.1084/jem.20011658

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Thymic Selection Generates a Large T Cell Pool Recognizing a Self-Peptide in Humans

Journal article published in 2002 by Alfred Zippelius ORCID, Mikaël J. Pittet, Pascal Batard, Nathalie Rufer, Magda de Smedt, M. De Smedt, Philippe Guillaume, Kim Ellefsen, Danila Valmori, Danielle Liénard, Jean Plum, H. Robson MacDonald, Hr Robson MacDonald, Daniel E. Speiser, Jean-Charles Cerottini and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The low frequency of self-peptide–specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single–positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults. Postthymic replicative history of Melan-A/MART-1–specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo. We provide direct evidence that the large T cell pool specific for the self-antigen Melan-A/MART-1 is mostly generated by thymic output of a high number of precursors. This represents the only known naive self-peptide–specific T cell repertoire directly accessible in humans.