Antibody Epitope Specificity for dsDNA Phosphate Backbone Is an Intrinsic Property of the Heavy Chain Variable Germline Gene Segment Used
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Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously produced anti-DNA antibody VH domain sequences supported our hypothesis only for antibodies, which use V gene segment in germline configuration, such as S57(VH31), MRL-DNA22, and VH11, members of the VH1 (J558) and VH7 (S107) gene families. The important finding is that out of seven V gene segments us...ed by spontaneous anti-DNA antibodies, F(0.367) is only expressed by the germline configuration of these three V gene segments. The data suggest that antibody specificity for the phosphate group moiety delineated as F(0.367) is the intrinsic property of the V germline gene segments used, whereas paratope/epitope interaction with antigens bearing this epitope, such as PC or dsDNA, requires corresponding antibody VH conformation that is susceptible to somatic mutation(s). © 2018 Srdic-Rajic, Kohler, Jurisic and Metlas.
Кључне речи:
anti-DNA antibodies / anti-PC antibodies / VH germline genes / Characterization of antibody specificity by ISM / dsDNA reactive antibodiesИзвор:
Frontiers in Immunology, 2018, 9, OCT, 2378-Финансирање / пројекти:
- Молекулске, биохемијске и имунолошке анализе у дијагностици тумора (RS-MESTD-Basic Research (BR or ON)-175056)
DOI: 10.3389/fimmu.2018.02378
ISSN: 1664-3224
WoS: 000447587300001
Scopus: 2-s2.0-85055173449
URI
https://www.frontiersin.org/article/10.3389/fimmu.2018.02378/fullhttps://vinar.vin.bg.ac.rs/handle/123456789/7929
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Институција/група
VinčaTY - JOUR AU - Srdić-Rajić, Tatjana AU - Kohler, Heinz V. AU - Jurišić, Vladimir AU - Metlaš, Radmila PY - 2018 UR - https://www.frontiersin.org/article/10.3389/fimmu.2018.02378/full UR - https://vinar.vin.bg.ac.rs/handle/123456789/7929 AB - Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously produced anti-DNA antibody VH domain sequences supported our hypothesis only for antibodies, which use V gene segment in germline configuration, such as S57(VH31), MRL-DNA22, and VH11, members of the VH1 (J558) and VH7 (S107) gene families. The important finding is that out of seven V gene segments used by spontaneous anti-DNA antibodies, F(0.367) is only expressed by the germline configuration of these three V gene segments. The data suggest that antibody specificity for the phosphate group moiety delineated as F(0.367) is the intrinsic property of the V germline gene segments used, whereas paratope/epitope interaction with antigens bearing this epitope, such as PC or dsDNA, requires corresponding antibody VH conformation that is susceptible to somatic mutation(s). © 2018 Srdic-Rajic, Kohler, Jurisic and Metlas. T2 - Frontiers in Immunology T1 - Antibody Epitope Specificity for dsDNA Phosphate Backbone Is an Intrinsic Property of the Heavy Chain Variable Germline Gene Segment Used VL - 9 IS - OCT SP - 2378 DO - 10.3389/fimmu.2018.02378 ER -
@article{ author = "Srdić-Rajić, Tatjana and Kohler, Heinz V. and Jurišić, Vladimir and Metlaš, Radmila", year = "2018", abstract = "Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously produced anti-DNA antibody VH domain sequences supported our hypothesis only for antibodies, which use V gene segment in germline configuration, such as S57(VH31), MRL-DNA22, and VH11, members of the VH1 (J558) and VH7 (S107) gene families. The important finding is that out of seven V gene segments used by spontaneous anti-DNA antibodies, F(0.367) is only expressed by the germline configuration of these three V gene segments. The data suggest that antibody specificity for the phosphate group moiety delineated as F(0.367) is the intrinsic property of the V germline gene segments used, whereas paratope/epitope interaction with antigens bearing this epitope, such as PC or dsDNA, requires corresponding antibody VH conformation that is susceptible to somatic mutation(s). © 2018 Srdic-Rajic, Kohler, Jurisic and Metlas.", journal = "Frontiers in Immunology", title = "Antibody Epitope Specificity for dsDNA Phosphate Backbone Is an Intrinsic Property of the Heavy Chain Variable Germline Gene Segment Used", volume = "9", number = "OCT", pages = "2378", doi = "10.3389/fimmu.2018.02378" }
Srdić-Rajić, T., Kohler, H. V., Jurišić, V.,& Metlaš, R.. (2018). Antibody Epitope Specificity for dsDNA Phosphate Backbone Is an Intrinsic Property of the Heavy Chain Variable Germline Gene Segment Used. in Frontiers in Immunology, 9(OCT), 2378. https://doi.org/10.3389/fimmu.2018.02378
Srdić-Rajić T, Kohler HV, Jurišić V, Metlaš R. Antibody Epitope Specificity for dsDNA Phosphate Backbone Is an Intrinsic Property of the Heavy Chain Variable Germline Gene Segment Used. in Frontiers in Immunology. 2018;9(OCT):2378. doi:10.3389/fimmu.2018.02378 .
Srdić-Rajić, Tatjana, Kohler, Heinz V., Jurišić, Vladimir, Metlaš, Radmila, "Antibody Epitope Specificity for dsDNA Phosphate Backbone Is an Intrinsic Property of the Heavy Chain Variable Germline Gene Segment Used" in Frontiers in Immunology, 9, no. OCT (2018):2378, https://doi.org/10.3389/fimmu.2018.02378 . .
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