We have examined the humoral and cellular responses of SLE patients to peptides based on the complementarity-determining regions (CDR) of a monoclonal anti-DNA antibody with a major idiotype- 16/6 Id, in comparison to their responses to the whole 16/6 Id-bearing antibody. Sera of 63% of the SLE patients had antibodies that bound the 16/6 Id, 80% had antibodies to one of the CDR-based peptides, and 40% of the patients reacted with both CDRs. Sera of only a few controls reacted with either the 16/6 Id (6%) or the CDR based peptides (4%) (P < 0.01). Peripheral blood lymphocytes (PBL) of 39% of the patients proliferated in response to the 16/6 Id or to one of the CDR-based peptides (37%), while in the control group the proliferation rates were 66% to the 16/6 Id and 59% to one of the CDR-based peptides (P < 0.05). The correlation between (both) the humoral and cellular immune responses to the CDR-based peptides and to the 16/6 Id suggests the relevance of these peptides to the 16/6 Id and provides additional information on the pathogenic moiety of the latter antibody.
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http://dx.doi.org/10.1023/a:1006685413157 | DOI Listing |
Curr Protoc
January 2023
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
The variable domain of the new antigen receptor (V ) of shark single domain antibodies is evolutionarily distant from the variable regions (V ) of mammalian immunoglobulins, yet it still has complementarity-determining regions (CDRs) that are involved in antigen recognition, therefore making it possible to humanize by grafting these CDRs to the framework of human V homologs. Here, we show the V CDR based on an analysis of currently available V -antigen structure complexes in the global Protein Data Bank archive of 3D structure data, and describe the detailed protocol to humanize V by CDR grafting, using B6 (an anti-Pseudomonas exotoxin V ), the most common type (Type II) of shark V s, as an example. Ongoing efforts will further optimize the protocol for moving shark V s to the clinic for treating cancer and other human diseases.
View Article and Find Full Text PDFBioorg Chem
February 2022
Research Group of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. Electronic address:
Monoclonal antibodies emerged as an important therapeutic drug class with remarkable specificity and binding affinity. Nonetheless, these heterotetrameric immunoglobulin proteins come with high manufacturing and therapeutic costs which can take extraordinary proportions, besides other limitations such as their limited in cellulo access imposed by their molecular size (ca. 150 kDa).
View Article and Find Full Text PDFBioorg Med Chem
July 2021
School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Outer Ring Road, Guangzhou 510006, China. Electronic address:
Covalent target modulation with small molecules has been emerging as a promising strategy for drug discovery. However, covalent inhibitory antibody remains unexplored due to the lack of efficient strategies to engineer antibody with desired bioactivity. Herein, we developed an intracellular selection method to generate covalent inhibitory antibody against human rhinovirus 14 (HRV14) 3C protease through unnatural amino acid mutagenesis along the heavy chain complementarity-determining region 3 (CDR-H3).
View Article and Find Full Text PDFFront Immunol
July 2019
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.
Mounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. While immunotherapies have shown a remarkable success in melanoma treatment, patients develop resistance by mechanisms that include the establishment of an immune suppressive tumor microenvironment.
View Article and Find Full Text PDFFront Microbiol
October 2012
Section of Microbiology, Department of Pathology and Laboratory Medicine, University of Parma Parma, Italy.
Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents.
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