CD8 surface levels alter the fate of α/β T cell receptor-expressing thymocytes in transgenic mice

Nancy A Lee, Dennis Y. Loh, Elizabeth Lacy

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

The mature T cell receptor (TCR) repertoire is established on the basis of discriminative events involving binding of the TCR α and β chains and CD4 or CD8 on immature thymocytes to major histocompatibility complex (MHC)/self-peptide complexes expressed in the thymus. To ask whether the strength of the interaction between a CD8/TCR complex and a MHC/self-peptide ligand plays a pivotal role in deciding the fate of a maturing thymocyte, we generated lines of transgenic mice that express distinct and elevated levels of CD8α, approximately 2, 3, and 6-10 times. These lines were then crossed to a transgenic line expressing the class I-restricted TCR, 2C. We found that thymocytes expressing the 2C TCR in combination with the highest levels of CD8 were deleted on the H-2 Kb background that is normally positively selecting for the 2C TCR. In contrast, thymocytes coexpressing the 2C TCR and moderately elevated levels of CD8 were selected for maturation. These results demonstrate directly that CD8 levels can affect the developmental fate of a maturing thymocyte and argue in support of an affinity model for thymocyte selection.

Original languageEnglish (US)
Pages (from-to)1013-1025
Number of pages13
JournalJournal of Experimental Medicine
Volume175
Issue number4
StatePublished - Apr 1 1992
Externally publishedYes

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Thymocytes
T-Cell Antigen Receptor
Transgenic Mice
Major Histocompatibility Complex
Peptides
Thymus Gland
Ligands

ASJC Scopus subject areas

  • Immunology

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CD8 surface levels alter the fate of α/β T cell receptor-expressing thymocytes in transgenic mice. / Lee, Nancy A; Loh, Dennis Y.; Lacy, Elizabeth.

In: Journal of Experimental Medicine, Vol. 175, No. 4, 01.04.1992, p. 1013-1025.

Research output: Contribution to journalArticle

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