| 1. |
- Andreasson, Ulrika, et al.
(författare)
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The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution
- 2006
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 362:2, s. 212-227
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Tidskriftsartikel (refereegranskat)abstract
- Upon encounter with antigen, the B lymphocyte population responds by producing a diverse set of antigen-specific antibodies of various isotypes. The vast size of the responding populations makes it very difficult to study clonal evolution and repertoire composition occurring during these processes in humans. Here, we have explored an approach utilizing the H-EPSILON-encoding transcriptome to investigate aspects of repertoire diversity during the season of antigen exposure. We show through sequencing of randomly picked transcripts that the sizes of patients' repertoires are relatively small. This specific aspect of the transcriptome allows us to construct evolutionary trees pinpointing features of somatic hypermutation as it occurs in humans. Despite the small size of the repertoires, they are highly diverse with respect to VDJ gene usage, suggesting that the H-EPSILON-encoding transcriptome is a faithful mimic of other class-switched isotypes. Importantly, it is possible to use antibody library and selection technologies to define the specificity of clonotypes identified by random sequencing. The small size of the H-EPSILON-encoding transcriptome of peripheral blood B cells, the simple identification of clonally related sets of genes in this population, and the power of library and selection technologies ensure that this approach will allow us to investigate antibody evolution in human B lymphocytes of known specificity. As H-EPSILON repertoires show many of the hallmarks of repertoires encoding other isotypes, we suggest that studies of this type will have an impact on our understanding of human antibody evolution even beyond that occurring in the IgE-producing B cell population.
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| 2. |
- Persson, Helena, et al.
(författare)
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A common idiotype in IgE and its relation to recognition of the grass pollen allergen Phl p 2.
- 2008
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Ingår i: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 45:9, s. 2715-2720
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Tidskriftsartikel (refereegranskat)abstract
- The variable regions of allergen-specific IgE, the isotype mediating allergic responses, are poorly defined to date. In this study we define the character of human antibody binding sites recognizing Phl p 2, a major allergen from timothy grass pollen. Independently raised specificities developed by phage display technology tended to have common sequence motifs (idiotypes), such as IGHV4-31 germline gene origin and heavy chain complementarity-determining region (CDR) 3 length and sequence. They also combined with highly related light chain sequences. Such heavy chain variable domain-encoding transcripts have also been found in the IgE-encoding transcriptome of yet other grass pollen allergic subjects. Altogether these data argue that a common idiotype is used to establish specific antibodies with a potential to mediate allergic responses to Phl p 2. Such a restriction may contribute to the limited molecular diversity observed in some IgE populations.
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