Peptide-MHC heterodimers reveal differential contribution of weak self-peptides to positive and negative selection
Abstract/Contents
- Abstract
- T cell central tolerance depends on the T cell receptor's affinity for self peptide/major histocompatibility complex, but how this affinity translates into the decision to mature or apoptose is unclear. In this body of work, we show that the OT-I TCR's affinity for its endogenous positively-selecting ligands, catnb/H-2Kb and cappa1/H-2Kb, is significantly lower than its previously reported affinity for artificial positively-selecting peptide/H-2Kbs. To understand how these extremely weak ligands produce signals in maturing thymocytes, we generated soluble monomeric and dimeric peptide/H-2Kb ligands. Monomeric agonist ovalbumin (ova)/Kb elicited no detectable signaling in OT-I thymocytes, but heterodimers of ova/Kb paired with an endogenous peptide/Kb induced very efficient deletion, for both positively-selecting and nonselecting endogenous peptides but not for an engineered 'null' partner peptide. In contrast, dimer-induced positive selection was much more sensitive to the identity of the partner peptide, because while catnb/Kb-catnb/Kb homodimers induced efficient positive selection, heterodimers of catnb/Kb paired with a nonselecting peptide/Kb could not induce selection, even though both ligands have measurable affinities for the OT-I TCR. Thus, both positive and negative selection can be driven by dimeric but not monomeric ligands, but positive selection has much more stringent requirements for the partner self-pMHC.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Juang, Jeremy Te-Hsun |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology |
| Primary advisor | Davis, Mark M |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Chien, Yueh-Hsiu |
| Thesis advisor | Garcia, K. Christopher |
| Thesis advisor | Nolan, Garry P |
| Advisor | Chien, Yueh-Hsiu |
| Advisor | Garcia, K. Christopher |
| Advisor | Nolan, Garry P |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jeremy Juang. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2012. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Jeremy Te-Hsun Juang
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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