Functional evidence for the recognition of endogenous peptides by autoreactive T cell clones

International Immunology
A D ReesR I Lechler

Abstract

The fine specificity of two human T cell clones responding to autologous HLA-DR1 expressing antigen-presenting cells (APC) in the absence of nominal antigen has been investigated using Epstein-Barr virus-transformed B cells (BCL) of known DR beta 1 domain sequence. It was found that responsiveness was markedly affected by changes in a limited number of residues in this domain. Substitution of the DR1 beta sequence at one residue, position 74, even conservatively, was found to be particularly significant. Located on the beta 1 domain alpha-helix, this residue is predicted to point into the antigen-binding groove and is therefore unlikely to make contact with the T cell receptor. This finding suggests that these T cells are specific for a bound endogenous peptide within the autologous major histocompatibility (MHC) binding groove. The autospecific T cell clones also responded to murine L cell transfectants expressing DR alpha DR1 beta as well as to transfectants expressing the mouse/human hybrid MHC molecule I-E alpha DR1 beta but not to the reciprocal combination DR alpha I-E beta, thus confirming the importance of the beta 1 domain to T cell recognition. In contrast to the autocytotoxicity observed with BCL, cytolysis of the mu...Continue Reading

Citations

Oct 3, 1998·Human Immunology·D OuA J Tingle
Jun 30, 2000·Endocrinology and Metabolism Clinics of North America·R S Bahn
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·B OngJ Newsom-Davis
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·H KropshoferH Kalbacher
Dec 1, 1990·Molecular and Cellular Probes·A D Rees

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