Abstract
Previous studies have demonstrated that an MHC class II molecule with an antigenic peptide genetically fused to its β-chain is capable of presenting this peptide to CD4+ T cells. We hypothesized that covalent peptide/class II complex may direct the accessory molecules to exert their function specifically onto T cells in a TCR-guided fashion. To test this hypothesis, we generated several recombinant adenoviruses expressing covalent myelin basic protein peptide/I-Au complex (MBP1-11/I-Au) and the costimulatory molecule B7-1. Functional studies demonstrated that adenovirus-infected cells are capable of activating an MBP1-11-specific T cell hybridoma. Coexpression of the B7-1 molecule and MBP1-11/I-Au by the same adenovirus leads to synergy in T cell activation elicited by virus-infected cells. Furthermore, studies in syngeneic mice infected with the various adenoviruses revealed that MBP1-11-specific T cells are specifically activated by the coexpression of B7-1 and MBP1-11/I-Au in vivo. In conclusion, the coexpression of the covalent peptide/class II complex and accessory molecules by the same adenovirus provides a unique strategy to modulate the epitope-specific T cell response in a TCR-guided fashion. This approach may be applicable to investigate the roles of other accessory molecules in the engagement of the TCR class II molecule by substituting B7-1 with other accessory molecules in the recombinant adenovirus.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1297-1305 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 167 |
| Issue number | 3 |
| State | Published - Aug 1 2001 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Recombinant adenovirus coexpressing covalent peptide/MHC class II complex and B7-1 : In vitro and in vivo activation of myelin basic protein-specific T cells. / Chen, J.; Huber, B. T.; Grand, R. J.; Li, Wei.
In: Journal of Immunology, Vol. 167, No. 3, 01.08.2001, p. 1297-1305.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Recombinant adenovirus coexpressing covalent peptide/MHC class II complex and B7-1
T2 - In vitro and in vivo activation of myelin basic protein-specific T cells
AU - Chen, J.
AU - Huber, B. T.
AU - Grand, R. J.
AU - Li, Wei
PY - 2001/8/1
Y1 - 2001/8/1
N2 - Previous studies have demonstrated that an MHC class II molecule with an antigenic peptide genetically fused to its β-chain is capable of presenting this peptide to CD4+ T cells. We hypothesized that covalent peptide/class II complex may direct the accessory molecules to exert their function specifically onto T cells in a TCR-guided fashion. To test this hypothesis, we generated several recombinant adenoviruses expressing covalent myelin basic protein peptide/I-Au complex (MBP1-11/I-Au) and the costimulatory molecule B7-1. Functional studies demonstrated that adenovirus-infected cells are capable of activating an MBP1-11-specific T cell hybridoma. Coexpression of the B7-1 molecule and MBP1-11/I-Au by the same adenovirus leads to synergy in T cell activation elicited by virus-infected cells. Furthermore, studies in syngeneic mice infected with the various adenoviruses revealed that MBP1-11-specific T cells are specifically activated by the coexpression of B7-1 and MBP1-11/I-Au in vivo. In conclusion, the coexpression of the covalent peptide/class II complex and accessory molecules by the same adenovirus provides a unique strategy to modulate the epitope-specific T cell response in a TCR-guided fashion. This approach may be applicable to investigate the roles of other accessory molecules in the engagement of the TCR class II molecule by substituting B7-1 with other accessory molecules in the recombinant adenovirus.
AB - Previous studies have demonstrated that an MHC class II molecule with an antigenic peptide genetically fused to its β-chain is capable of presenting this peptide to CD4+ T cells. We hypothesized that covalent peptide/class II complex may direct the accessory molecules to exert their function specifically onto T cells in a TCR-guided fashion. To test this hypothesis, we generated several recombinant adenoviruses expressing covalent myelin basic protein peptide/I-Au complex (MBP1-11/I-Au) and the costimulatory molecule B7-1. Functional studies demonstrated that adenovirus-infected cells are capable of activating an MBP1-11-specific T cell hybridoma. Coexpression of the B7-1 molecule and MBP1-11/I-Au by the same adenovirus leads to synergy in T cell activation elicited by virus-infected cells. Furthermore, studies in syngeneic mice infected with the various adenoviruses revealed that MBP1-11-specific T cells are specifically activated by the coexpression of B7-1 and MBP1-11/I-Au in vivo. In conclusion, the coexpression of the covalent peptide/class II complex and accessory molecules by the same adenovirus provides a unique strategy to modulate the epitope-specific T cell response in a TCR-guided fashion. This approach may be applicable to investigate the roles of other accessory molecules in the engagement of the TCR class II molecule by substituting B7-1 with other accessory molecules in the recombinant adenovirus.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035423254&partnerID=8YFLogxK
M3 - Article
C2 - 11466346
AN - SCOPUS:0035423254
VL - 167
SP - 1297
EP - 1305
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -