Identification and sequence analysis of a novel HLA-B*3936 allele / 中国实验血液学杂志

The aim of study was to confirm the novel HLA allele HLA-B*3936 in Chinese population and to analyze its sequence. The proband was a cord blood donor in the Zhejiang province. DNA was extracted from whole blood by PEL-FREEZ DNA extraction kit. The amplification of HLA-B exons 2 - 4 of the proband was performed by allele specific primer PCR and the amplified product was sequenced bidirectionally with primers. The sequencing results showed HLA-B alleles of the proband as B*4002 and the novel allele. The sequences of the novel allele have been submitted to GenBank (DQ242650, DQ242651, DQ242652). After Blast HLA analysis, the novel allele showed four nucleotide differences with HLA-B*3901 at nucleotide position 527 T-->A, 538 C-->T, 539 T-->G, 544 A-->G in exon 3. It resulted in three amino acid change from Val to Glu at codon 152, Ile to Trp at codon 156, Thr to Ala at codon 158. The result suggested that this allele is a novel allele and has been officially named HLA-B*3936 by the WHO Nomenclature Committee.

Generation of Renal Cell Carcinoma-specific CD4+ /CD8+ T Cells Restricted by an HLA-39 from a RCC Patient Vaccinated with GM-CSF Gene-Transduced Tumor Cells

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene- transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines. METHODS: To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific CD8+ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma (IFNgamma), and cloned by limiting dilution. RESULTS: Among several RCC-specific cytotoxic T lymphocytes (CTLs), a CD4+ /CD8+ double positive T cell clone (17/A2) appeared to recognize IFNgamma-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after IFNgamma treatment. CONCLUSION: These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by IFNgamma.