McCormick, David;
(1998)
Characterisation of and T cell responses to the P91A tumour minus antigen.
Doctoral thesis (Ph.D.), University College London.
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Abstract
The P91A tumour minus (tum-) antigen is a tumour specific transplantation antigen expressed on the P815 derivative cell line P91. The tumour minus form of the P91A protein has a single amino acid substitution in comparison to the wild-type protein due to a single base change in the P91A tum-gene. As a result of this amino acid substitution a unique H2-Ld binding peptide is generated and recognised in complex with H2-Ld by CD8+ cytotoxic T cells. P91A transgenic DBA/2 mice have been previously generated. Transgenic and non-transgenic mice differ only in expression of the P91A epitope. P91A peptide specific T cell responses have been examined in P91A transgenic and non-transgenic mice. T cells responsive to low concentrations of P91A peptide are present in non-transgenic mice while high concentrations of peptide are required to elicit equivalent proliferative responses in P91A transgenic mice. These results suggest that high affinity P91A specific T cells may have been deleted in P91A transgenic mice. P91A specific T cell clones have been generated from P91A transgenic and non-transgenic mice and their T cell receptor usage and sequence examined. Where possible this data has been correlated with recognition of the H2- Ld-P91A peptide complex. To further evaluate the interaction between P91A specific T cells and the P91A epitope the exact nature of the naturally processed P91A epitope has been determined and MHC and TCR contact residues defined. The P91A epitope is an octamer peptide which binds to Ld in the absence of consensus binding motif residues. Finally, using a series of P91A based minigenes evidence has been gained which suggests that the P91A epitope can be generated from P91A protein fragments which are targeted to the endoplasmic reticulum.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Characterisation of and T cell responses to the P91A tumour minus antigen. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10102197 |
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