title: (Altered) self peptides and the regulation of self reactivity in the peripheral T cell pool.
abstract: Tolerance for self has appeared incomplete for many self antigens. We have obtained experimental evidence that both for self heat shock proteins and T cell receptor V-gene products, reactive T cells are part of the normal immune repertoire. Furthermore, it has become apparent that stimulation of T cell responsiveness to these antigens, by using peptide immunisation or by transfer of activated T cells, raises resistance to experimentally induced autoimmune arthritis. In addition, available evidence has suggested that these reactivities may be functional during natural processes of disease remission. The observations with regard to heat-shock proteins have indicated that mechanism leading to disease resistance are most efficiently triggered by exposing the immune system to non-self antigens such as bacterial hsp's, which are similar to, but not identical to, self. Experimental evidence has been obtained, that conserved bacterial hsp peptides, may trigger self hsp reactive T cells, with disease suppressive regulatory potential. It is possible that such self hsp reactive T cells, being expanded by recognising bacterial peptides as full agonists, do, in fact, perceive the self epitopes as partial agonists, and therefore have the possibility of displaying downregulatory activity at the site of inflammation. Experiments with peptide analogs of self epitopes, being variants of disease critical T cell epitopes, have indeed suggested that also their activity in modulating disease may comply with the principles of dominant immunological tolerance.
authors.affiliation: Department of Immunology, Utrecht University, Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Van Eden
authors.forename: S M
authors.initials: SM
authors.lastname: Anderton
authors.forename: R
authors.initials: R
authors.lastname: Van Der Zee
authors.forename: B J
authors.initials: BJ
authors.lastname: Prakken
authors.forename: C P
authors.initials: CP
authors.lastname: Broeren
authors.forename: M H
authors.initials: MH
authors.lastname: Wauben
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002648:Child; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell