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.
Artículo
en Chino
| 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>
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Oligopéptidos
/
Región Variable de Inmunoglobulina
/
Reordenamiento Génico
/
Antígenos HLA-A
/
Antígeno HLA-A2
/
Linfoma de Burkitt
/
Cadenas Pesadas de Inmunoglobulina
/
Linfocitos T CD8-positivos
/
Epítopos de Linfocito T
/
Biología Celular
Tipo de estudio:
Estudio pronóstico
Límite:
Adolescente
/
Niño
/
Child, preschool
/
Humanos
/
Lactante
Idioma:
Chino
Revista:
Chinese Journal of Oncology
Año:
2005
Tipo del documento:
Artículo
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