Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor

Jonathan Kaye, Mei Ling Hsu, Marie Elizabeth Sauron, Stephen C. Jameson, Nicholas R.J. Gascoigne, Stephen M. Hedrick

Research output: Contribution to journalArticlepeer-review

622 Scopus citations

Abstract

T LYMPHOCYTES are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC). There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus. As a result of this positive selection, thymocytes that express antigen receptors with a threshold affinity for self MHC-encoded glycoproteins preferentially emigrate from the thymus and seed peripheral lymphoid organs. The specificity for both foreign antigen and MHC molecules is imparted by the α and β chains of the T-cell antigen receptor (TCR). Two other T-cell surface proteins, CD4 and CD8, which bind non-polymorphic regions of class II and class I MHC molecules respectively, are also involved in these recognition events and play an integral role in thymic selection. In order to elucidate the developmental pathways of class II MHC-rest rioted T cells in relation to these essential accessory molecules, we have produced TCR-transgenic mice expressing a receptor specific for a fragment of pigeon cytochrome c and the Ek (class II MHC) molecule. The transgenic TCR is expressed on virtually all T cells in mice expressing Ek. The thymuses of these mice contain an abnormally high percentage of mature CD4+CD8- cells. In addition, the peripheral T-cell population is almost exclusively CD4+, demonstrating that the MHC specificity of the TCR determines the phenotype of T cells during selection in the thymus.

Original languageEnglish (US)
Pages (from-to)746-749
Number of pages4
JournalNature
Volume341
Issue number6244
DOIs
StatePublished - 1989

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