Molecular mimics can induce a nonautoaggressive repertoire that preempts induction of autoimmunity.
To determine the role that competition plays in a molecular mimic's capacity to induce autoimmunity, we studied the ability of naïve encephalitogenic T cells to expand in response to agonist altered peptide ligands (APLs), some capable of stimulating both self-directed and exclusively APL-specific T cells. Our results show that although the APLs capable of stimulating exclusively APL-specific T cells are able to expand encephalitogenic T cells in vitro, the encephalitogenic repertoire is effectively outcompeted in vivo when the APL is used as the priming immunogen. Competition as a mechanism was supported by: (i) the demonstration of a population of exclusively APL-specific T cells, (ii) an experiment in which an encephalitogenic T cell population was successfully outcompeted by adoptively transferred naïve T cells, and (iii) demonstrating that the elimination of competing T cells bestowed an APL with the ability to expand naïve encephalitogenic T cells in vivo. In total, these experiments support the existence of a reasonably broad T cell repertoire responsive to a molecular mimic (e.g., a microbial agent), of which the exclusively mimic-specific component tends to focus the immune response on the invading pathogen, whereas the rare cross-reactive, potentially autoreactive T cells are often preempted from becoming involved.
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. emaverakis@yahoo.com
Emanual
E
Maverakis
Juscilene S
JS
Menezes
Akio
A
Ametani
Mei
M
Han
David B
DB
Stevens
Yong
Y
He
Yan
Y
Wang
Yoko
Y
Ono
Yoshinori
Y
Miyamura
Kit S
KS
Lam
E Sally
ES
Ward
Eli E
EE
Sercarz
D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005434:Flow Cytometry; D007114:Immunization; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D009842:Oligopeptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell