Title :
N332-Directed broadly neutralizing antibodies use diverse modes of HIV-1 recognition: inferences from heavy-light chain complementation of function
Abstract :
- Dozens of broadly neutralizing HIV-1 antibodies have been isolated in the last few years from the sera of HIV-1-infected individuals
- Only a limited number of regions on the HIV-1 spike, however, are recognized by these antibodies
- One of these regions ( N332 ) is characterized by an N-linked glycan at residue 332 on HIV-1 gp120 and is recognized by antibody 2G12 and by the recently reported antibodies PGT121-137, the latter isolated from three donors
- To investigate the diversity in mode of antibody recognition at the N332 site , we used functional complementation between antibody heavy and light chains as a means of assessing similarity in mode of recognition
- We examined a matrix of 12 PGT-heavy chains with each of 12 PGT-light chains
- Expression in 96-well format for the 144 antibodies (132 chimeric and 12 wild-type) was generally consistent (58 ± 10 µg/ml)
- In contrast, recognition of HIV-1 gp120 was bimodal: when the source of heavy and light chains was from the same donor, recognition was good; when sources of heavy and light chains were from different donors, recognition was poor
- Moreover, neutralization of HIV-1 strains SF162.LS and TRO .11 generally followed patterns of gp120 recognition
- These results are consistent with published sequence , mutational, and structural findings, all of which indicate that N332-directed neutralizing antibodies from different donors utilize different modes of recognition, and provide support for a correlation between functional complementation of antibody heavy and light chains and similarity in antibody mode of recognition
- Overall , our results add to the growing body of evidence that the human immune system is capable of recognizing the N332-region of HIV-1 gp120 in diverse ways