Haematologica 2003 - Supplements

Haematologica 2003 - Supplements Haematologica 2003 - Supplements

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13.11.2014 Views

cells (LI=7.3%). This contrasts with the major (88%) population of non-proliferating (LI=1.3%, p

esponse and have demonstrated that CD8+ cells can recognise shared immunoglobulin-derived peptides bound to MHC class I molecules. (6) Thus, it may be possible to develop a small set of shared peptides capable of inducing a T cell response in a range of patients. Certainly the ability to predict immunodominant peptides has significant implications for vaccination strategies in the treatment of all B-cell malignancies. We have recently used this method to predict immunodominant peptides from the sequence of the CDR3 region of the IgH gene of 16 patients with myeloma. (1) CDR3 peptides from most patients failed to achieve a BIMAS score of 100, suggesting that the poor affinity between the unique peptides and the patient's HLA would fail to generate a significant T cell response. As most immunodominant peptides in other B cell malignancies were found outside the CDR3 region (6) and more often in framework regions, future studies in patients with myeloma should not expect that immunodominant peptides with the potential to stimulate anti-tumour T cell activity will only be found in the CDR3 region. 4. Identification of idiotype-specific T cells using MHC Class I Tetramers MHC tetrameric complexes offer the possibility to identify and manipulate peptide specific T cells. We have sequenced the hypervariable regions of both the heavy and light chain hypervariable regions of 6 patients with expanded CD8+ clones, used bioinformatics to demonstrate that only 3 of the six patients had immunodominant idiotypic peptides and prepared tetrameric MHC class I complexes containing CDR-derived immunodominant peptides to search for idiotype-specific T cells in the blood of the 2 surviving patients. Initial studies which failed to detect tetramer positive cells in either patient suggested that idiotype-specific T cells were deleted. Modified staining techniques demonstrated that tetramer positive T cells comprised 1-10% of an IL-2 activated T cell population (

cells (LI=7.3%). This contrasts with the major (88%) population<br />

of non-proliferating (LI=1.3%, p

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