Correction: Identification of a naturally processed cyclin D1 T‐helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry (Vol. 34(12) 2004, p. 3644–3651)

Due to a technical error, the name of the second author, Patrice Decker, was unfortunately omitted from the Table of contents of the December 2004 issue. We apologize for any inconvenience caused. DOI 10.1002/eji.200425510     

DNA测序鉴定新等位基因HLA-DRB1*1609

目的 鉴定HLA新等位基因DRB1＊1609。方法 应用分子克隆和DNA测序的技术测定HLA新等位基因的核苷酸序列，进行HLA等位基因序列比对分析和新等位基因的血清学分型及家系分析。结果 新等位基因DRB1第二外显子（exon2，Ex2）序列与所有已知的HLA等位基因序列均不相同，与同源性最高的HLA-DRB1＊160101相比，第127位碱基由A→T，引起相应编码第47位氨基酸由酪氨酸Tyr（Y）→苯丙氨酸Phe（F）。血清学分型表明抗原特异性为DR16。家系分析提示该志愿者DRB1＊1609等位基因遗传自母亲。结论 DNA测序表明被测标本含有HLA-DRB1新等位基因，被WHOHLA因子命名委员会正式命名为HLA-DRB1＊1609。     

Possible impact of HLA class I and class II on malignancies driven by a single germ-line BRCA1 mutation

This study provides the first immunogenetic preliminary evidence that specific human leucocyte antigen (HLA) class I and class II alleles and haplotypes may be relevant for BRCA1 c.5263_5264insC driven oncogenesis. Observed HLA associations might have practical implications for establishment of predictive markers for the response to immunotherapies in malignancies driven by this germ-line mutation.     

The serodominant secreted effector protein of Salmonella,SseB, is a strong CD4 antigen containing an immunodominant epitope presented by diverse HLA class II alleles

Detailed characterization of the protective T‐cell response in salmonellosis is a pressing unmet need in light of the global burden of human Salmonella infections and the likely contribution of CD4 T cells to immunity against this intracellular infection. In previous studies screening patient sera against antigen arrays, SseB was noteworthy as a serodominant target of adaptive immunity, inducing significantly raised antibody responses in HIV‐seronegative compared with seropositive patients. SseB is a secreted protein, part of the Espa superfamily, localized to the bacterial surface and forming part of the translocon of the type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2. We demonstrate here that SseB is also a target of CD4 T‐cell immunity, generating a substantial response after experimental infection in human volunteers, with around 0·1% of the peripheral repertoire responding to it. HLA‐DR/peptide binding studies indicate that this protein encompasses a number of peptides with ability to bind to several different HLA‐DR alleles. Of these, peptide 11 (p11) was shown in priming of both HLA‐DR1 and HLA‐DR4 transgenic mice to contain an immunodominant CD4 epitope. Analysis of responses in human donors showed immunity focused on p11 and another epitope in peptide 2. The high frequency of SseB‐reactive CD4 T cells and the broad applicability to diverse HLA genotypes coupled with previous observations of serodominance and protective vaccination in mouse challenge experiments, make SseB a plausible candidate for next‐generation Salmonella vaccines.     

Design of a ProDer f 1 vaccine delivered by the MHC class II pathway of antigen presentation and analysis of the effectiveness for specific immunotherapy

Dermatophagoides farinae (Der f 1) is one of leading cause for allergic asthma, and allergen-specific immunotherapy (SIT) is currently recognized as the only etiological therapy to ameliorate asthmatic symptom. The current study was designed on the major histocompatibility complex (MHC) class II pathway, invariant chain (Ii)-segment hybrids as vaccine basis to explore the efficacy of Der f 1 hybrid vaccine by virtue of Ii as carrier in enhancing the protective immune response to asthma. Initially, we engineered a fused molecule, DCP-IhC-ProDer f 1, to deliver ProDer f 1 antigen via specific dendritic cell-targeting peptides to dendritic cells (DCs). Then the DCP-IhC-ProDer f 1 was immunized to the asthmatic models of murine induced by ProDer f 1 allergen. The findings showed that the cytokine repertoire in the murine model was shifted after SIT, including stronger secretion of IFN-γ and IL-10, and a decreased production of IL-4 and IL-17. ELISA determination revealed that the hybrid displayed weak IgE and IgG₁ reactivities, and IgG_2a levels were elevated. Furthermore, DCP-IhC-ProDer f 1 treatment inhibited inflammatory cell infiltration in the lung tissues. Our results suggest that the DCP-Ihc-ProDer f 1 may be used as a candidate SIT against asthma.     

Aberrant splicing at catalytic site as cause of infantile onset glycogen storage disease type II (GSDII): Molecular identification of a novel IVS9 (+2GT→GC) in combination with rare IVS10 (+1GT→CT)

Glycogen storage disease type II (GSDII) results from deleterious mutations in acid α‐glucosidase gene. To date several mutant alleles have been studied including missense and nonsense mutations, insertions, small and large deletions as well as splice site mutations. Apart from IVS1 (? 13→G), 525delT, and Δ18, the other mutations are rare and often unique to single patients. Moreover, the molecular findings also observed in the different ethnic groups makes it difficult to attempt to correlate genotype and phenotype to explain the origin of clinical variability. Even though there are no conclusive genotype phenotype correlations, the in frame splice site mutations identified up until now have been found associated with the juvenile/adult onset of GSDII. In this study we describe a novel in frame splicing defect, IVS9 (+2GT→GC), identified in combination with the rare IVS10 (+1GT→CT) mutation in a patient with classic infantile GSDII disease. Because both mutations occur at the catalytic site region, it is likely that the alteration of both catalytic function and steric conformation of the enzyme may be responsible for the most severe form of the disease. © 2001 Wiley‐Liss, Inc.