Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans.
Interactions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR) control natural killer cell (NK) functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susc...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-10-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3814319?pdf=render |
| _version_ | 1819088429089030144 |
|---|---|
| author | Paul J Norman Jill A Hollenbach Neda Nemat-Gorgani Lisbeth A Guethlein Hugo G Hilton Marcelo J Pando Kwadwo A Koram Eleanor M Riley Laurent Abi-Rached Peter Parham |
| author_facet | Paul J Norman Jill A Hollenbach Neda Nemat-Gorgani Lisbeth A Guethlein Hugo G Hilton Marcelo J Pando Kwadwo A Koram Eleanor M Riley Laurent Abi-Rached Peter Parham |
| author_sort | Paul J Norman |
| collection | DOAJ |
| description | Interactions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR) control natural killer cell (NK) functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susceptibility. Although studied at low-resolution in many populations, high-resolution analysis of combinatorial diversity of HLA class I and KIR is limited to Asian and Amerindian populations with low genetic diversity. At the other end of the spectrum is the West African population investigated here: we studied 235 individuals, including 104 mother-child pairs, from the Ga-Adangbe of Ghana. This population has a rich diversity of 175 KIR variants forming 208 KIR haplotypes, and 81 HLA-A, -B and -C variants forming 190 HLA class I haplotypes. Each individual we studied has a unique compound genotype of HLA class I and KIR, forming 1-14 functional ligand-receptor interactions. Maintaining this exceptionally high polymorphism is balancing selection. The centromeric region of the KIR locus, encoding HLA-C receptors, is highly diverse whereas the telomeric region encoding Bw4-specific KIR3DL1, lacks diversity in Africans. Present in the Ga-Adangbe are high frequencies of Bw4-bearing HLA-B*53:01 and Bw4-lacking HLA-B*35:01, which otherwise are identical. Balancing selection at key residues maintains numerous HLA-B allotypes having and lacking Bw4, and also those of stronger and weaker interaction with LILRB1, a KIR-related receptor. Correspondingly, there is a balance at key residues of KIR3DL1 that modulate its level of cell-surface expression. Thus, capacity to interact with NK cells synergizes with peptide binding diversity to drive HLA-B allele frequency distribution. These features of KIR and HLA are consistent with ongoing co-evolution and selection imposed by a pathogen endemic to West Africa. Because of the prevalence of malaria in the Ga-Adangbe and previous associations of cerebral malaria with HLA-B*53:01 and KIR, Plasmodium falciparum is a candidate pathogen. |
| first_indexed | 2024-12-21T21:51:54Z |
| format | Article |
| id | doaj.art-3503166ed6d044509432b12c89929605 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-21T21:51:54Z |
| publishDate | 2013-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-3503166ed6d044509432b12c899296052022-12-21T18:49:04ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-10-01910e100393810.1371/journal.pgen.1003938Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans.Paul J NormanJill A HollenbachNeda Nemat-GorganiLisbeth A GuethleinHugo G HiltonMarcelo J PandoKwadwo A KoramEleanor M RileyLaurent Abi-RachedPeter ParhamInteractions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR) control natural killer cell (NK) functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susceptibility. Although studied at low-resolution in many populations, high-resolution analysis of combinatorial diversity of HLA class I and KIR is limited to Asian and Amerindian populations with low genetic diversity. At the other end of the spectrum is the West African population investigated here: we studied 235 individuals, including 104 mother-child pairs, from the Ga-Adangbe of Ghana. This population has a rich diversity of 175 KIR variants forming 208 KIR haplotypes, and 81 HLA-A, -B and -C variants forming 190 HLA class I haplotypes. Each individual we studied has a unique compound genotype of HLA class I and KIR, forming 1-14 functional ligand-receptor interactions. Maintaining this exceptionally high polymorphism is balancing selection. The centromeric region of the KIR locus, encoding HLA-C receptors, is highly diverse whereas the telomeric region encoding Bw4-specific KIR3DL1, lacks diversity in Africans. Present in the Ga-Adangbe are high frequencies of Bw4-bearing HLA-B*53:01 and Bw4-lacking HLA-B*35:01, which otherwise are identical. Balancing selection at key residues maintains numerous HLA-B allotypes having and lacking Bw4, and also those of stronger and weaker interaction with LILRB1, a KIR-related receptor. Correspondingly, there is a balance at key residues of KIR3DL1 that modulate its level of cell-surface expression. Thus, capacity to interact with NK cells synergizes with peptide binding diversity to drive HLA-B allele frequency distribution. These features of KIR and HLA are consistent with ongoing co-evolution and selection imposed by a pathogen endemic to West Africa. Because of the prevalence of malaria in the Ga-Adangbe and previous associations of cerebral malaria with HLA-B*53:01 and KIR, Plasmodium falciparum is a candidate pathogen.http://europepmc.org/articles/PMC3814319?pdf=render |
| spellingShingle | Paul J Norman Jill A Hollenbach Neda Nemat-Gorgani Lisbeth A Guethlein Hugo G Hilton Marcelo J Pando Kwadwo A Koram Eleanor M Riley Laurent Abi-Rached Peter Parham Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. PLoS Genetics |
| title | Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. |
| title_full | Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. |
| title_fullStr | Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. |
| title_full_unstemmed | Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. |
| title_short | Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. |
| title_sort | co evolution of human leukocyte antigen hla class i ligands with killer cell immunoglobulin like receptors kir in a genetically diverse population of sub saharan africans |
| url | http://europepmc.org/articles/PMC3814319?pdf=render |
| work_keys_str_mv | AT pauljnorman coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT jillahollenbach coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT nedanematgorgani coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT lisbethaguethlein coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT hugoghilton coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT marcelojpando coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT kwadwoakoram coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT eleanormriley coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT laurentabirached coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans AT peterparham coevolutionofhumanleukocyteantigenhlaclassiligandswithkillercellimmunoglobulinlikereceptorskirinageneticallydiversepopulationofsubsaharanafricans |