| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Abdool Karim, Quarraisha Lambson, Bronwen E. Berrie, Leigh Morris, Lynn Naicker, Dshanta Jackson, Katherine J. L. Abdool Karim, Salim S. Scheepers, Cathrine Wright, Imogen A. Goosen, Mark Ismail, Arshad Moore, Penny L. Travers, Simon A. Shrestha, Ram K. Garrett, Nigel |
| Description |
Author Affiliation: Scheepers C ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa); Shrestha RK ( South African National Bioinformatics Institute, South African Medical Research Council Bioinformatics Unit, University of the Western Cape, Bellville 7535, South Africa); Lambson BE ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa); Jackson KJ ( School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia); Wright IA ( South African National Bioinformatics Institute, South African Medical Research Council Bioinformatics Unit, University of the Western Cape, Bellville 7535, South Africa); Naicker D ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa); Goosen M ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa); Berrie L ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa); Ismail A ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa); Garrett N ( Centre for the AIDS Programme of Research in South Africa, KwaZulu-Natal 4013, South Africa); Abdool Karim Q ( Centre for the AIDS Programme of Research in South Africa, KwaZulu-Natal 4013, South Africa); Abdool Karim SS ( Centre for the AIDS Programme of Research in South Africa, KwaZulu-Natal 4013, South Africa); Moore PL ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa); Travers SA ( South African National Bioinformatics Institute, South African Medical Research Council Bioinformatics Unit, University of the Western Cape, Bellville 7535, South Africa); Morris L ( Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa) |
| Abstract |
The human Ig repertoire is vast, producing billions of unique Abs from a limited number of germline Ig genes. The IgH V region (IGHV) is central to Ag binding and consists of 48 functional genes. In this study, we analyzed whether HIV-1-infected individuals who develop broadly neutralizing Abs show a distinctive germline IGHV profile. Using both 454 and Illumina technologies, we sequenced the IGHV repertoire of 28 HIV-infected South African women from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 and 004 cohorts, 13 of whom developed broadly neutralizing Abs. Of the 259 IGHV alleles identified in this study, approximately half were not found in the International Immunogenetics Database (IMGT). This included 85 entirely novel alleles and 38 alleles that matched rearranged sequences in non-IMGT databases. Analysis of the rearranged H chain V region genes of mAbs isolated from seven of these women, as well as previously isolated broadly neutralizing Abs from other donors, provided evidence that at least eight novel or non-IMGT alleles contributed to functional Abs. Importantly, we found that, despite a wide range in the number of IGHV alleles in each individual, including alleles used by known broadly neutralizing Abs, there were no significant differences in germline IGHV repertoires between individuals who do and do not develop broadly neutralizing Abs. This study reports novel IGHV repertoires and highlights the importance of a fully comprehensive Ig database for germline gene usage prediction. Furthermore, these data suggest a lack of genetic bias in broadly neutralizing Ab development in HIV-1 infection, with positive implications for HIV vaccine design. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1500118 |
| Journal |
The Journal of Immunology |
| Issue Number |
9 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-05-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antibodies, Neutralizing Genes, Immunoglobulin Germ Cells Metabolism Hiv Antibodies Genetics Immunology Hiv Infections Hiv-1 African Continental Ancestry Group Alleles Immunoglobulin Heavy Chains Immunoglobulin Variable Region Phylogeny Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
