Positive and negative selection of an antigen receptor on T cells in transgenic mice

William C. Sha, Christopher A. Nelson, Rodney D. Newberry, David M. Kranz, John H. Russell, Dennis Y. Loh

Research output: Contribution to journalArticlepeer-review

703 Scopus citations

Abstract

The T-cell repertoire found in the periphery is thought to be shaped by two developmental events in the thymus that involve the antigen receptors of T lymphocytes. First, interactions between T cells and major histocompatibility complex (MHC) molecules select a T-cell repertoire skewed towards recognition of antigens in the context of self-MHC molecules1-5. In addition, T cells that react strongly to self-MHC molecules are eliminated by a process called self-tolerance6-10. We have recently described transgenic mice expressing the αβ T-cell receptor from the cytotoxic T lymphocyte 2C (ref. 11). The clone 2C was derived from a BALB.B (H-2b) anti-BALB/c (H-2d) mixed lymphocyte culture and is specific for the Ld class I MHC antigen. In transgenic H-2b mice, a large fraction of T cells in the periphery expressed the 2C T-cell receptor. These T cells were predominantly CD4-CD8+ and were able to specifically lyse target cells bearing Ld. We now report that in the periphery of transgenic mice expressing Ld, functional T cells bearing the 2C T-cell receptor were deleted. This elimination of autoreactive T cells appears to take place at or before the CD4+CD8+ stage in thymocyte development. In addition, we report that in H-2s mice, a non-autoreactive target haplotype, large numbers of CD8+ T cells bearing the 2C T-cell receptor were not found, providing strong evidence for the positive selection of the 2C T-cell receptor specificity by H-2b molecules.

Original languageEnglish
Pages (from-to)73-76
Number of pages4
JournalNature
Volume336
Issue number6194
DOIs
StatePublished - 1988

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