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The Impact of Self-Tolerance on the Polyclonal CD8⁺ T Cell Repertoire¹

Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

TCRs possess considerable cross-reactivity toward structurally related Ags. Because the signaling threshold for negative selection is lower than that required for activation of mature T cells, the question arises as to which extent thymic deletion of self-specific T cells affects T cell responsiveness toward foreign peptides. In this study we show, in three different mouse models systems, that the polyclonal CD8⁺ T cell repertoire has a marked ability to react against the majority of Ags related to self despite self-tolerance, even in cases where self and foreign differ only marginally at a single TCR-contact residue. Thus, while individual T cells are markedly cross-reactive, the ability to distinguish between closely related Ags is introduced at the polyclonal T cell level.

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The JI 2004 172: 1989-1990. [Full Text]  

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				M. J. Turner, E. R. Jellison, E. G. Lingenheld, L. Puddington, and L. Lefrancois Avidity maturation of memory CD8 T cells is limited by self-antigen expression J. Exp. Med., August 4, 2008; 205(8): 1859 - 1868. [Abstract] [Full Text] [PDF]