| Title: |
Peptides derived from the whole sequence of BCR‐ABL bind to several class I molecules allowing specific induction of human cytotoxic T lymphocytes |
| Authors: |
Buzyn, Agnès; Ostankovitch, Marina; Zerbib, Anne; Kemula, Mathilde; Connan, Francine; Varet, Bruno; Guillet, Jean‐Gérard; Choppin, Jeannine |
| Source: |
European Journal of Immunology ; volume 27, issue 8, page 2066-2072 ; ISSN 0014-2980 1521-4141 |
| Publisher Information: |
Wiley |
| Publication Year: |
1997 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Chronic myeloid leukemia (CML) is characterized cytogenetically by a t(9;22) translocation which generates a hybrid bcr‐abl gene, encoding a p210 bcr‐abl fusion protein. The induction in vitro of leukemia‐specific T cells reactive with p210 bcr‐abl is a strategy developed for an immunological therapeutic approach in CML. Peptides from the junction region of this chimeric protein have been considered as potential targets for a cytotoxic response against leukemic cells. However, only a few peptides encompassing the two p210 bcr‐abl breakpoints have been shown to bind to the most common HLA class I molecules, which limits the number of patients who could benefit from this approach. We assume that the presence of chimeric BCR‐ABL protein in leukemic cells may affect processing and delivery of peptides, possibly giving rise to new epitopes at the cell surface. We selected 162 peptides from the whole sequence of this protein, including 14 peptides of the b2a2 and b3a2 junctions, which had an anchor motif for a common HLA class I molecule. We tested their ability to bind to eight HLA class I molecules (HLA‐A1, ‐A2, ‐A3, ‐A11, ‐B7, ‐B8, ‐B27, ‐B44). We identified 48 peptides from outside the junction region, with intermediate or strong binding capacities to these HLA class I molecules contrasting with only six junction peptides with a moderate binding capacity to HLA‐A3/A11, ‐B8, or ‐B44 molecules. Moreover, cytotoxic T lymphocyte lines specific for various peptides outside the junction were generated from peripheral blood mononuclear cells of HLA‐A2 or ‐B7 healthy donors and from one CML patient. These results contribute to evaluation of immunity to the BCR‐ABL chimeric protein. Further studies are required to investigate whether such epitopes are correctly processed and presented by leukemic cells. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/eji.1830270834 |
| Availability: |
https://doi.org/10.1002/eji.1830270834; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Feji.1830270834; https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.1830270834 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.8225604E |
| Database: |
BASE |