It is now clear that antigen presenting cells (APCs) do not present all the possible peptides of self-proteins to the immune system. When then, is the fate of T cells specific for those self-peptides that escape processing? In this study, the COOH-terminal peptide (residues 81-104) of self cytochrome c (cyt c) elicited strong autoimmune T cells, as well as autoantibodies specific for this immunogen. These T cells did not respond to stimulation with the whole self cyt c molecule, demonstrating that APCs cannot process and present the self 81-104 peptide. Whereas mice were unresponsive to immunization with the whole mouse cyt c molecule, the mouse 81-104 fragment together with the whole self-molecule induced and amplified the autoimmune T cell response to sites within the 1-80 peptide. T cells that never contact the relevant self-peptide are functionally ignorant. They do not become tolerized or deleted, nor do they normally participate in immune responses to the native whole self-protein, since APCs cannot present the 81-104 peptide.
Article| February 01 1993
The inability to process a self-peptide allows autoreactive T cells to escape tolerance.
M J Mamula
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1993) 177 (2): 567–571.
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M J Mamula; The inability to process a self-peptide allows autoreactive T cells to escape tolerance.. J Exp Med 1 February 1993; 177 (2): 567–571. doi: https://doi.org/10.1084/jem.177.2.567
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