Autor: |
Abe R; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892., Ishida Y, Yui K, Katsumata M, Chused TM |
Jazyk: |
angličtina |
Zdroj: |
The Journal of experimental medicine [J Exp Med] 1992 Aug 01; Vol. 176 (2), pp. 459-68. |
DOI: |
10.1084/jem.176.2.459 |
Abstrakt: |
Shaping of the T cell repertoire by selection during intrathymic maturation involves T cell receptor (TCR) recognition of major histocompatibility complex/self-antigen complexes. In this communication, we studied the ability of minor lymphocyte stimulating (Mls) determinants to act as self-tolerogens in the selection of the T cell repertoire. We demonstrate that unprimed T cells from normal as well as TCR transgenic mice form Mls-specific conjugates with antigen-presenting cells, and that this TCR-ligand interaction leads to elevation of intercellular Ca2+ ([Ca2+]i). Peripheral T cells from TCR transgenic mice expressing receptors specific for self-Mls antigen show no reactivities to Mlsa. However, a proportion of immature thymocytes from these mice show specific binding and strong [Ca2+]i elevation in response to self-antigen-presenting cells, although these thymocytes do not proliferate. This self-reactivity of thymocytes is inhibited by antibodies specific for TCR, CD4, CD8, class II molecules, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1. These results demonstrate for the first time that before thymic negative selection, immature T cells can specifically interact with cells bearing self-antigen, and suggest that the resulting TCR-dependent signal transduction events provide a basis for negative selection of self-reactive T cells. |
Databáze: |
MEDLINE |
Externí odkaz: |
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