Abstract
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., amicrobial 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2550-2555 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | 6 |
| DOIs | |
| State | Published - Feb 9 2010 |
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Keywords
- Autoimmune
- Driver clones
- Experimental autoimmune encephalomyelitis
- Molecular mimicry
- Multiple sclerosis
ASJC Scopus subject areas
- General
Cite this
Molecular mimics can induce a nonautoaggressive repertoire that preempts induction of autoimmunity. / Maverakis, Emanual Michael; Menezes, Juscilene S.; Ametani, Akio; Han, Mei; Stevens, David B.; He, Yong; Wang, Yan; Ono, Yoko; Miyamura, Yoshinori; Lam, Kit; Ward, E. Sally; Sercarz, Eli E.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 6, 09.02.2010, p. 2550-2555.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular mimics can induce a nonautoaggressive repertoire that preempts induction of autoimmunity
AU - Maverakis, Emanual Michael
AU - Menezes, Juscilene S.
AU - Ametani, Akio
AU - Han, Mei
AU - Stevens, David B.
AU - He, Yong
AU - Wang, Yan
AU - Ono, Yoko
AU - Miyamura, Yoshinori
AU - Lam, Kit
AU - Ward, E. Sally
AU - Sercarz, Eli E.
PY - 2010/2/9
Y1 - 2010/2/9
N2 - 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., amicrobial 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.
AB - 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., amicrobial 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.
KW - Autoimmune
KW - Driver clones
KW - Experimental autoimmune encephalomyelitis
KW - Molecular mimicry
KW - Multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=77249092530&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77249092530&partnerID=8YFLogxK
U2 - 10.1073/pnas.0914508107
DO - 10.1073/pnas.0914508107
M3 - Article
C2 - 20133742
AN - SCOPUS:77249092530
VL - 107
SP - 2550
EP - 2555
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 6
ER -