کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2831167 1163782 2013 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate
چکیده انگلیسی

Methylene diphenyl diisocyanate (MDI), a low molecular weight chemical important for producing polyurethane foam, coatings, and elastomers is a major cause of occupational asthma, however, mechanisms of disease pathogenesis remain poorly understood. This study characterizes the rearranged germline and hypervariable region cDNA of new anti-MDI secreting hybridomas derived from mice immunized with MDI-conjugated to autologous serum proteins. Six IgG1 secreting clones were identified in initial screening ELISAs, based on differential binding to MDI conjugated human albumin vs. mock exposed albumin. The mAbs secreted by the hybridomas also recognized MDI conjugated to other model proteins (e.g. ovalbumin, transferrin), but did not bind unconjugated proteins, or protein conjugates prepared with other isocyanates (e.g. TDI, HDI). The mAbs displayed MDI-dose dependent binding in ELISA and Western blot, and exhibited varying degrees of cross-competition, suggesting differences in epitope specificity. The cDNA encoding the monoclonal antibodies reveal clonal differences in the CDR3 regions, germline gene usage, and patterns of somatic hypermutation related to epitope specificity. Together, the data provide new insight into the molecular determinants of humoral MDI specificity, and characterize anti-MDI IgG1 mAbs that may be developed into useful diagnostic reagents.


► 1st IgG mAbs made against occupational allergen methylene-diphenyl-diisocyanate (MDI).
► cDNA of anti-MDI mAbs reveal clonally distinct origins.
► Homology in CDR3 suggests antigen-driven selection for certain amino acids.
► New anti-MDI mAbs should be useful diagnostic reagents for biomonitoring MDI exposure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 54, Issue 2, June 2013, Pages 233–237
نویسندگان
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