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Immunogenetic factors driving formation of ultralong VH CDR3 in Bos taurus antibodies

Cellular & Molecular Immunology 2019年第1期16卷 53-64页

作者： Thaddeus C Deiss Melissa Vadnais Feng Wang Patricia L Chen Ali Torkamani Waithaka Mwangi Marie-Paule Lefranc Michael F Criscitiello Vaughn V Smider Comparative Immunogenetics Laboratory Department of Veterinary PathobiologyCollege of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843USA Department of Molecular Medicine The Scripps Research InstituteLa JollaCA 92037USA California Institute for Biomedical Research La JollaCA 92037USA Department of Integrative Structural and Computational Biology The Scripps Research InstituteLa JollaCA 92037USA Department of Diagnostic Medicine and Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKS 66506USA IMGT the International ImMunoGeneTics information systemLaboratoire d’ImmunoGénétique MoléculaireInstitut de Génétique HumaineCNRSUniversity of MontpellierMontpellier 34396France Department of Microbial Pathogenesis and Immunology College of MedicineTexas A&M UniversityBryanTX 77807USA Fabrus Inc.La JollaCA 92037USA

The antibody repertoire of Bos taurus is characterized by a subset of variable heavy(VH)chain regions with ultralong third complementarity determining regions(CDR3)which,compared to other species,can provide a potent response to challenging antigens like HIV *** unusual CDR3 can range to over seventy highly diverse amino acids in length and form uniqueβ-ribbon‘stalk’and disulfide bonded‘knob’structures,far from the typical antigen binding *** genetic components and processes for forming these unusual cattle antibody VH CDR3 are not well *** we analyze sequences of Bos taurus antibody VH domains and find that the subset with ultralong CDR3 exclusively uses a single variable gene,IGHV1-7(VHBUL)rearranged to the longest diversity gene,*** eight nucleotide duplication at the 3′end of IGHV1-7 encodes a longer V-region producing an extended Fβ-strand that contributes to the stalk in a rearranged CDR3.A low amino acid variability was observed in CDR1 and CDR2,suggesting that antigen binding for this subset most likely only depends on the *** a novel,potentially AID mediated,deletional diversification mechanism of the *** VH ultralong CDR3 knob was discovered,in which interior codons of the IGHD8-2 region are removed while maintaining integral structural components of the knob and descending strand of the stalk in *** deletions serve to further diversify cysteine positions,and thus disulfide bonded ***,both germline and somatic genetic factors and processes appear to be involved in diversification of this structurally unusual cattle VH ultralong CDR3 repertoire.

关键词： bovine complementarity determining region 3 repertoire diversification deletions immunoglobulin heavy chain

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CDR3 repertoire diversity of CD8+ T lymphocytes in patients with HCV

CDR3 repertoire diversity of CD8+ T lymphocytes in patients ...

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第十三届全国免疫学学术大会

作者： Yu Ping Mengjia Song Meng Wanng Zhiqin Li Yi Zhang the First Affiliated Hospital of Zhengzhou University

T cell receptors(TCR) diversity is known to serve as a defining hallmark of the antigen-reactive T cell repertoire. complementarity determining region 3(CDR3) was the most important region for the recognition of peptide-major histocompatibility complex(MHC) complexes and represented the diversity of TCR repertoire. In this study, we detected the CDR3 spectratypes by complexity scoring system to assess TCR repertoire diversity and further analyzed the correlation of CDR3 score with CD8 T cell function and with the prognosis of chronic hepatitis C virus(HCV)-infected patients. The results demonstrated that CDR3 score was related to CD8 T cell function and prognosis by analyzing the clinical indicators such as viral load(VL), rapid virologic response(RVR), early virologic response(EVR) and sustained virologic response(SVR). Importantly, we found that Vb27, a member of CDR3 subfamily, might play an important role in the clearance of HCV. These findings indicate that TCR diversity maybe serve as a biomarker to predict the clinical parameters of HCV-infected patients.

关键词： T cell receptor CD8 T cells complementarity determining region 3 TCR diversity TCR repertoire

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