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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>
Subject(s)
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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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