PMC:5118421 / 31041-32765 JSONTXT

{"project":"TEST0","denotations":[{"id":"27920779-170-176-3100261","span":{"begin":649,"end":651},"obj":"[\"11859119\"]"},{"id":"27920779-84-90-3100262","span":{"begin":1390,"end":1392},"obj":"[\"22407974\"]"}],"text":"This result alone, however, did not provide insight regarding the potential value of antinuclear activity generated via SHM. Our analyses of X-ray structures of Ag–Ab complexes also did not shed light on this question because we examined complexes involving only protein Ags. However, our sequence analyses of antiviral antibodies did reveal a considerable variation in the relative frequency with which an AGY codon mutated to encode an Arg codon versus a codon for Asn or Thr. Based on triplet mutability indices and base preference targeting by AID, we would expect a ~2:1 ratio favoring mutations to Asn/Thr codons over mutations to Arg codons (13). Overall, the Asn + Thr/Arg ratio was 2.7:1 among combined antiviral antibodies, suggesting some selection pressure against Arg. However, there was considerable variation among different antiviral antibodies. For example, while the 2:1 ratio closely approximated that seen for antibodies to hepatitis virus, the ratio was ~3.5:1 for antibodies against influenza. It is unclear whether deviations from the expected ratio are due to the autoreactive properties of CDR Arg residues or simply due to direct Ag-contact considerations. Arg is larger than Asn or Thr, such that replacing Ser with Arg may impede Ag engagement more often due to steric effects. Results of our analysis together with those of a prior study by Raghunathan et al. (19), however, indicate that Arg residues in Ab V regions frequently make contact with protein Ags. Thus, regardless of whether Ab affinity for nuclear Ags is beneficial to some viral immune responses, somatic mutations that produce Arg codons at germline CDR AGY codons can be beneficial to the development of high-avidity antibodies."}

{"project":"2_test","denotations":[{"id":"27920779-11859119-34707984","span":{"begin":649,"end":651},"obj":"11859119"},{"id":"27920779-22407974-34707985","span":{"begin":1390,"end":1392},"obj":"22407974"}],"text":"This result alone, however, did not provide insight regarding the potential value of antinuclear activity generated via SHM. Our analyses of X-ray structures of Ag–Ab complexes also did not shed light on this question because we examined complexes involving only protein Ags. However, our sequence analyses of antiviral antibodies did reveal a considerable variation in the relative frequency with which an AGY codon mutated to encode an Arg codon versus a codon for Asn or Thr. Based on triplet mutability indices and base preference targeting by AID, we would expect a ~2:1 ratio favoring mutations to Asn/Thr codons over mutations to Arg codons (13). Overall, the Asn + Thr/Arg ratio was 2.7:1 among combined antiviral antibodies, suggesting some selection pressure against Arg. However, there was considerable variation among different antiviral antibodies. For example, while the 2:1 ratio closely approximated that seen for antibodies to hepatitis virus, the ratio was ~3.5:1 for antibodies against influenza. It is unclear whether deviations from the expected ratio are due to the autoreactive properties of CDR Arg residues or simply due to direct Ag-contact considerations. Arg is larger than Asn or Thr, such that replacing Ser with Arg may impede Ag engagement more often due to steric effects. Results of our analysis together with those of a prior study by Raghunathan et al. (19), however, indicate that Arg residues in Ab V regions frequently make contact with protein Ags. Thus, regardless of whether Ab affinity for nuclear Ags is beneficial to some viral immune responses, somatic mutations that produce Arg codons at germline CDR AGY codons can be beneficial to the development of high-avidity antibodies."}

{"project":"MyTest","denotations":[{"id":"27920779-11859119-34707984","span":{"begin":649,"end":651},"obj":"11859119"},{"id":"27920779-22407974-34707985","span":{"begin":1390,"end":1392},"obj":"22407974"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"This result alone, however, did not provide insight regarding the potential value of antinuclear activity generated via SHM. Our analyses of X-ray structures of Ag–Ab complexes also did not shed light on this question because we examined complexes involving only protein Ags. However, our sequence analyses of antiviral antibodies did reveal a considerable variation in the relative frequency with which an AGY codon mutated to encode an Arg codon versus a codon for Asn or Thr. Based on triplet mutability indices and base preference targeting by AID, we would expect a ~2:1 ratio favoring mutations to Asn/Thr codons over mutations to Arg codons (13). Overall, the Asn + Thr/Arg ratio was 2.7:1 among combined antiviral antibodies, suggesting some selection pressure against Arg. However, there was considerable variation among different antiviral antibodies. For example, while the 2:1 ratio closely approximated that seen for antibodies to hepatitis virus, the ratio was ~3.5:1 for antibodies against influenza. It is unclear whether deviations from the expected ratio are due to the autoreactive properties of CDR Arg residues or simply due to direct Ag-contact considerations. Arg is larger than Asn or Thr, such that replacing Ser with Arg may impede Ag engagement more often due to steric effects. Results of our analysis together with those of a prior study by Raghunathan et al. (19), however, indicate that Arg residues in Ab V regions frequently make contact with protein Ags. Thus, regardless of whether Ab affinity for nuclear Ags is beneficial to some viral immune responses, somatic mutations that produce Arg codons at germline CDR AGY codons can be beneficial to the development of high-avidity antibodies."}