The effects of limiting the T cell repertoire in the mouse
Abstract/Contents
- Abstract
- T cells will usually recognize any pathogen that threatens the body, despite the many different and constantly changing forms these pathogens can take. This is accomplished by the enormous diversity of T-cell receptors that are randomly generated during T-cell maturation. There are a number of distinct mechanisms that drive this diversity: one is the recombination of gene segments, (designated V, D, and J), from pools of many possible gene segments. Another is the addition and deletion of nucleotides at the gene segments joints (between the V, D, and J segments). This yields ~10^15 different possible T-cell receptors, which is many times greater that the number of T cells in the periphery of either mice (~10^8) or humans (~10^11). The T-cell receptor is formed from two polypeptide chains, [alpha] and [beta], each derived from separately rearranged gene segments. Each chain is composed of semi-randomly chosen gene segments. We utilized three transgenes, one limiting the [alpha] chain and two limiting the [beta] chain. These progressively limited the number available gene segments of 100 V[alpha]'s to 1; 50 J[alpha]'s to 2; 30 V[beta]'s to 1; 2D[beta]'s to 1 and 13 J[beta]'s to 2. This reduced the number of gene segment combinations from a theoretical 3,900,000 to 4 combinations. The addition and deletion of nucleotides at the gene segment joints is unaffected. In an in vivo CTL killing assay, the mice with these limited T cell repertoires are able to recognize most but not all of the antigenic peptides tested (9 of 11, in the most restricted mice). Their immunity to Listeria monocytogenes was reduced somewhat; but the LD50 of Yersinia pseudotuberculosis was not diminished by limiting T-cell repertoire, and viral load after murine cytomegalovirus infection was similar to wild type. The limited repertoire mice also exhibited less vigorous alloreactive responses to some haplotypes, indicating that alloreactive responses are influenced by V gene segment compatibility with the MHC. We conclude that N and P nucleotide addition is sufficient for the bulk of T-cell immunity, at least in the laboratory setting. Limiting V(D)J gene segment choice, despite eliminating some T-cell specificities, does not have a dramatic effect on T-cell immunity.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Campbell, Jeff Dennis |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Davis, Mark M |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Garcia, K. Christopher |
| Thesis advisor | Jones, Patricia |
| Thesis advisor | McDevitt, Hugh O |
| Advisor | Garcia, K. Christopher |
| Advisor | Jones, Patricia |
| Advisor | McDevitt, Hugh O |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jeff Dennis Campbell. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Jeff Dennis Campbell
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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