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TY - JOUR AU - Sha, William C. AU - Nelson, Christopher A. AU - Newberry, Rodney D. AU - Kranz, David M. AU - Russell, John H. AU - Loh, Dennis Y. PY - 1988 DA - 1988/11/01 TI - Positive and negative selection of an antigen receptor on T cells in transgenic mice JO - Nature SP - 73 EP - 76 VL - 336 IS - 6194 AB - 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–28 mice, a non-autoreactive target haplotype, large numbers of CDS* 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. SN - 1476-4687 UR - https://doi.org/10.1038/336073a0 DO - 10.1038/336073a0 ID - Sha1988 ER -