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-Structure paper
タイトル | Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 2190, Year 2019 |
掲載日 | 2019年5月16日 |
著者 | Cassandra A Simonich / Laura Doepker / Duncan Ralph / James A Williams / Amrit Dhar / Zak Yaffe / Lauren Gentles / Christopher T Small / Brian Oliver / Vladimir Vigdorovich / Vidya Mangala Prasad / Ruth Nduati / D Noah Sather / Kelly K Lee / Frederick A Matsen Iv / Julie Overbaugh / |
PubMed 要旨 | HIV-infected infants develop broadly neutralizing plasma responses with more rapid kinetics than adults, suggesting the ontogeny of infant responses could better inform a path to achievable vaccine ...HIV-infected infants develop broadly neutralizing plasma responses with more rapid kinetics than adults, suggesting the ontogeny of infant responses could better inform a path to achievable vaccine targets. Here we reconstruct the developmental lineage of BF520.1, an infant-derived HIV-specific broadly neutralizing antibody (bnAb), using computational methods developed specifically for this purpose. We find that the BF520.1 inferred naive precursor binds HIV Env. We also show that heterologous cross-clade neutralizing activity evolved in the infant within six months of infection and that, ultimately, only 2% SHM is needed to achieve the full breadth of the mature antibody. Mutagenesis and structural analyses reveal that, for this infant bnAb, substitutions in the kappa chain were critical for activity, particularly in CDRL1. Overall, the developmental pathway of this infant antibody includes features distinct from adult antibodies, including several that may be amenable to better vaccine responses. |
リンク | Nat Commun / PubMed:31097697 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.8 Å |
構造データ | |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / Complex / Broadly neutralizing antibody |