Epitopes recognized by cytotoxic T lymphocytes in immunoglobulin heavy chain variable regions expressed by B-cell acute lymphoblastic leukemia / 中华肿瘤杂志
Chinese Journal of Oncology
;
(12): 106-110, 2005.
Article
in Chinese
| WPRIM
| ID: wpr-331216
ABSTRACT
<p><b>OBJECTIVE</b>To clone IgHV genes from childhood B-ALL cells and identify CTL epitopes deduced from IgHV gene.</p><p><b>METHODS</b>Seven IgHV gene families were respectively amplified by PCR and directly sequenced for 37 childhood B-ALL cases. Bioinformatics were applied for analyzing characteristics of sequences available and predicting HLA-A*0201 molecule-binding nonapeptides derived from IgHV. The predicted nonapeptide QLVQSGAEV was synthesized and its binding affinity to T2 cells determined. CD8+ T cells from a healthy HLA-A*0201+ donor peripheral blood were stimulated repeatedly with QLVQSGAEV-loaded antigen presenting cells.</p><p><b>RESULTS</b>IgHV gene rearrangements were identified in 37 B-ALL. Forty IgHV gene sequences available preferentially utilized V(H)4-59 and V(H)4-34 gene segments. Increased frequency (15.4%) of D7-27 in B-ALL IgHV was found compared to that reported for adult PBLs (P = 0.02); 20.0% DJ(H) junctions in B-ALL lacked non-encoding nucleotides, a frequency higher than that reported for adult PBLs (P = 0.02). 17.5% B-ALL IgHV contained < 2% replacement mutations. Forty B-ALL IgHV sequences acquired 12 high HLA-A*0201-binding nonapeptides, 10 (83.0%) peptides were located in frame region (FR)1 and 3. The synthesized peptide QLVQSGAEV up-regulated HLA-A*0201 expression 1.63 fold on the surface of T2 cells. The frequency of QLVQSGAEV-specific CD8+ T cells in a healthy HLA-A*0201+ donor peripheral blood increased from 1.6% and 82.6% after two-round and 3-round stimulations, respectively.</p><p><b>CONCLUSION</b>IgHV genes in childhood B-ALL are of germline characteristics. Their heavy chain framework regions contain HLA-A*0201-binding nonapeptides. These peptides are capable of inducing specific CD8+ T cells to activate and proliferate.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oligopeptides
/
Immunoglobulin Variable Region
/
Gene Rearrangement
/
HLA-A Antigens
/
HLA-A2 Antigen
/
Burkitt Lymphoma
/
Immunoglobulin Heavy Chains
/
CD8-Positive T-Lymphocytes
/
Epitopes, T-Lymphocyte
/
Cell Biology
Type of study:
Prognostic study
Limits:
Adolescent
/
Child
/
Child, preschool
/
Humans
/
Infant
Language:
Chinese
Journal:
Chinese Journal of Oncology
Year:
2005
Type:
Article
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