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Differential Reactivity of Germ Line Allelic Variants of a Broadly Neutralizing HIV-1 Antibody to a gp41 Fusion Intermediate Conformation.
- Source :
-
Journal of Virology . Nov2011, Vol. 85 Issue 22, p1-2. 2p. - Publication Year :
- 2011
-
Abstract
- Genetic factors, as well as antigenic stimuli, can influence antibody repertoire formation. Moreover, the affinity of antigen for unmutated naïve B cell receptors determines the threshold for activation of germinal center antibody responses. The gp41 2F5 broadly neutralizing antibody (bNAb) uses the VH2-5 gene, which has 10 distinct alleles that use either a heavy-chain complementaritydetermining region 2 (HCDR2) aspartic acid (DH54) or an HCDR2 asparagine (NH54) residue. The 2F5 HCDR2 DH54 residue has been shown to form a salt bridge with gp41 665K; the VH2-5 germ line allele variant containing NH54 cannot do so and thus should bind less avidly to gp41. Thus, the induction of 2F5 bNAb is dependent on both genetic and structural factors that could affect antigen affinity of unmutated naïve B cell receptors. Here, we studied allelic variants of the VH2-5 inferred germ line forms of the HIV-1 gp41 bNAb 2F5 for their antigen binding affinities to gp41 linear peptide and conformational protein antigens. Both VH2-5 2F5 inferred germ line variants bound to gp41 peptides and protein, including the fusion intermediate protein mimic, although more weakly than the mature 2F5 antibody. As predicted, the affinity of the NH54 variant for fusion-intermediate conformation was an order of magnitude lower than that of the DH54 VH2-5 germ line antibody, demonstrating that allelic variants of 2F5 germ line antibodies differentially bind to gp41. Thus, these data demonstrate a genetically determined trait that may affect host responses to HIV-1 envelope epitopes recognized by broadly neutralizing antibodies and has implications for unmutated ancestor-based immunogen design. [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMMUNOGLOBULINS
*CELL membranes
*CELL receptors
*LYMPHOCYTES
*EPITOPES
Subjects
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 85
- Issue :
- 22
- Database :
- Academic Search Index
- Journal :
- Journal of Virology
- Publication Type :
- Academic Journal
- Accession number :
- 68938968
- Full Text :
- https://doi.org/10.1128/JVI.05680-11