TY - JOUR
T1 - Next-generation sequencing reveals new insights about gene usage and CDR-H3 composition in the horse antibody repertoire
AU - Manso, Taciana Conceição
AU - Groenner-Penna, Michele
AU - Minozzo, João Carlos
AU - Antunes, Bruno Cesar
AU - Ippolito, Gregory C.
AU - Molina, Franck
AU - Felicori, Liza F.
N1 - Funding Information:
This research was supported by Brazilian Funding Agencies: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) , Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq ).
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/1
Y1 - 2019/1
N2 - Horse serum antibodies have been used for greater than a century for the treatment and prophylaxis of infectious diseases and envenomations. Little is known, however, about the immunogenetic diversity that produces horse serum antibodies. Here, we employed next-generation sequencing for a first-in-kind comprehensive analysis of the equine B-cell repertoire. Nearly 45,000 and 30,000 clonotypes were obtained for the heavy-chain (IGH) and lambda light-chain (IGL) loci, respectively. We observed skewed use of the common subgroups IGHV2 (92.49%) and IGLV8 (82.50%), consistent with previous reports, but also novel use of the rare genes IGHV6S1 and IGLV4S2. CDR-H3 amino acid composition revealed different amino acid patterns at positions 106 and 116 compared to human, rabbit, and mouse, suggesting that an extended conformation predominates among horse CDR-H3 loops. Our analysis provides new insights regarding the mechanisms employed to generate antibody diversity in the horse, and could be applicable to the optimized design of synthetic antibodies intended for future therapeutic use.
AB - Horse serum antibodies have been used for greater than a century for the treatment and prophylaxis of infectious diseases and envenomations. Little is known, however, about the immunogenetic diversity that produces horse serum antibodies. Here, we employed next-generation sequencing for a first-in-kind comprehensive analysis of the equine B-cell repertoire. Nearly 45,000 and 30,000 clonotypes were obtained for the heavy-chain (IGH) and lambda light-chain (IGL) loci, respectively. We observed skewed use of the common subgroups IGHV2 (92.49%) and IGLV8 (82.50%), consistent with previous reports, but also novel use of the rare genes IGHV6S1 and IGLV4S2. CDR-H3 amino acid composition revealed different amino acid patterns at positions 106 and 116 compared to human, rabbit, and mouse, suggesting that an extended conformation predominates among horse CDR-H3 loops. Our analysis provides new insights regarding the mechanisms employed to generate antibody diversity in the horse, and could be applicable to the optimized design of synthetic antibodies intended for future therapeutic use.
KW - Antibody repertoire
KW - CDR-H3 composition
KW - Diversity
KW - Horse
KW - Immunoglobulin
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U2 - 10.1016/j.molimm.2018.11.017
DO - 10.1016/j.molimm.2018.11.017
M3 - Article
C2 - 30562645
AN - SCOPUS:85058390564
SN - 0161-5890
VL - 105
SP - 251
EP - 259
JO - Molecular Immunology
JF - Molecular Immunology
ER -