scholarly journals HLA-DQ-Specific Recombinant Human Monoclonal Antibodies Allow for In-Depth Analysis of HLA-DQ Epitopes

2022 ◽  
Vol 12 ◽  
Author(s):  
Suzanne Bezstarosti ◽  
Cynthia S. M. Kramer ◽  
Marry E. I. Franke-van Dijk ◽  
Manon Vergunst ◽  
Kim H. Bakker ◽  
...  
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibodies ◽  
Memory B Cells ◽  
Human Monoclonal Antibodies ◽  
Specific Memory ◽  
Hla Dq ◽  
Depth Analysis ◽  
Single Antigen ◽  
Donor Specific Antibodies ◽  
Hla Molecules

HLA-DQ donor-specific antibodies (DSA) are the most prevalent type of DSA after renal transplantation and have been associated with eplet mismatches between donor and recipient HLA. Eplets are theoretically defined configurations of surface exposed amino acids on HLA molecules that require verification to confirm that they can be recognized by alloantibodies and are therefore clinically relevant. In this study, we isolated HLA-DQ specific memory B cells from immunized individuals by using biotinylated HLA-DQ monomers to generate 15 recombinant human HLA-DQ specific monoclonal antibodies (mAb) with six distinct specificities. Single antigen bead reactivity patterns were analyzed with HLA-EMMA to identify amino acids that were uniquely shared by the reactive HLA alleles to define functional epitopes which were mapped to known eplets. The HLA-DQB1*03:01-specific mAb LB_DQB0301_A and the HLA-DQB1*03-specific mAb LB_DQB0303_C supported the antibody-verification of eplets 45EV and 55PP respectively, while mAbs LB_DQB0402_A and LB_DQB0602_B verified eplet 55R on HLA-DQB1*04/05/06. For three mAbs, multiple uniquely shared amino acid configurations were identified, warranting further studies to define the inducing functional epitope and corresponding eplet. Our unique set of HLA-DQ specific mAbs will be further expanded and will facilitate the in-depth analysis of HLA-DQ epitopes, which is relevant for further studies of HLA-DQ alloantibody pathogenicity in transplantation.

scholarly journals Analysis of Human Monoclonal Antibodies Generated by Dengue Virus-Specific Memory B Cells

2012 ◽  
Vol 25 (5) ◽  
pp. 348-359 ◽  
Author(s):  
Heather Friberg ◽  
Smita Jaiswal ◽  
Kim West ◽  
Marvin O'Ketch ◽  
Alan L. Rothman ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cells ◽  
Dengue Virus ◽  
Memory B Cells ◽  
Human Monoclonal Antibodies ◽  
Specific Memory

scholarly journals Human monoclonal antibodies by immortalization of memory B cells

2007 ◽  
Vol 18 (6) ◽  
pp. 523-528 ◽  
Author(s):  
Antonio Lanzavecchia ◽  
Davide Corti ◽  
Federica Sallusto
Keyword(s):  
Monoclonal Antibodies ◽  
B Cells ◽  
Memory B Cells ◽  
Human Monoclonal Antibodies

scholarly journals Subclade 2.2.1-Specific Human Monoclonal Antibodies That Recognize an Epitope in Antigenic Site A of Influenza A(H5) Virus HA Detected between 2015 and 2018

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 321
Author(s):  
Moe Okuda ◽  
Seiya Yamayoshi ◽  
Ryuta Uraki ◽  
Mutsumi Ito ◽  
Taiki Hamabata ◽  
...  
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibodies ◽  
Influenza A ◽  
Antigenic Site ◽  
Influenza Viruses ◽  
Interspecies Transmission ◽  
Single Amino Acid ◽  
Human Monoclonal Antibodies ◽  
Highly Pathogenic ◽  
H5n1 Vaccine

Highly pathogenic avian H5 influenza viruses persist among poultry and wild birds throughout the world. They sometimes cause interspecies transmission between avian and mammalian hosts. H5 viruses possessing the HA of subclade 2.3.4.4, 2.3.2.1, 2.2.1, or 7.2 were detected between 2015 and 2018. To understand the neutralizing epitopes of H5-HA, we characterized 15 human monoclonal antibodies (mAbs) against the HA of H5 viruses, which were obtained from volunteers who received the H5N1 vaccine that contains a subclade 2.2.1 or 2.1.3.2 virus as an antigen. Twelve mAbs were specific for the HA of subclade 2.2.1, two mAbs were specific for the HA of subclade 2.1.3.2, and one mAb was specific for the HA of both. Of the 15 mAbs analyzed, nine, which were specific for the HA of subclade 2.2.1, and shared the VH and VL genes, possessed hemagglutination inhibition and neutralizing activities, whereas the others did not. A single amino acid substitution or insertion at positions 144–147 in antigenic site A conferred resistance against these nine mAbs to the subclade 2.2.1 viruses. The amino acids at positions 144–147 are highly conserved among subclade 2.2.1, but differ from those of other subclades. These results show that the neutralizing epitope including amino acids at positions 144–147 is targeted by human antibodies, and plays a role in the antigenic difference between subclade 2.2.1 and other subclades.

scholarly journals mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

2021 ◽  
Author(s):  
Zijun Wang ◽  
Fabian Schmidt ◽  
Yiska Weisblum ◽  
Frauke Muecksch ◽  
Christopher O. Barnes ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Protein S ◽  
Memory B Cells ◽  
Receptor Binding Domain ◽  
Cell Responses ◽  
Specific Memory ◽  
Vesicular Stomatitis

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3–6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

scholarly journals Human Monoclonal Antibodies Derived From Memory B Cells Following Live Attenuated Dengue Virus Vaccination or Natural Infection Exhibit Similar Characteristics

2013 ◽  
Vol 207 (12) ◽  
pp. 1898-1908 ◽  
Author(s):  
Scott A. Smith ◽  
Ruklanthi de Alwis ◽  
Nurgun Kose ◽  
Anna P. Durbin ◽  
Stephen S. Whitehead ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cells ◽  
Dengue Virus ◽  
Natural Infection ◽  
Memory B Cells ◽  
Human Monoclonal Antibodies ◽  
Virus Vaccination
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