Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein

Author:

Kyobe Samuel1ORCID,Mwesigwa Savannah12,Nkurunungi Gyaviira34ORCID,Retshabile Gaone5ORCID,Egesa Moses34ORCID,Katagirya Eric2ORCID,Amujal Marion2ORCID,Mlotshwa Busisiwe C.5,Williams Lesedi5,Sendagire Hakim1, ,Kiragga Dithan6,Mardon Graeme78,Matshaba Mogomotsi910,Hanchard Neil A.11,Kyosiimire-Lugemwa Jacqueline3ORCID,Robinson David12ORCID

Affiliation:

1. Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala P.O. Box 7072, Uganda

2. Department of Immunology and Molecular Biology, College of Health Sciences, Makerere University, Kampala P.O. Box 7072, Uganda

3. The Medical Research Council/Uganda Virus Research Institute & London School Hygine Tropical Medicine Uganda Research Unit, Entebbe P.O. Box 49, Uganda

4. Department of Infection Biology, London School of Hygiene & Tropical Medicine, Keppel Street London, London WC1E 7HT, UK

5. Department of Biological Sciences, University of Botswana, Gaborone Private Bag UB 0022, Botswana

6. Baylor College of Medicine Children’s Foundation, Kampala P.O. Box 72052, Uganda

7. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA

8. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA

9. Pediatric Retrovirology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA

10. Botswana-Baylor Children’s Clinical Centre of Excellence, Gaborone Private Bag BR 129, Botswana

11. National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA

12. Department of Chemistry and Forensics, School of Science and Technology, Nottingham Trent University Clifton Lane, Nottingham NG11 8NS, UK

Abstract

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02 CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope potentially restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Funder

NIH Common Fund H3Africa Initiative

Makerere University-Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training

Makerere University Research and Innovations Fund

Africa Foundation to the Developing Excellence in Leadership

DELTAS Africa

Bill & Melinda Gates Foundation

Gilead Sciences

Publisher

MDPI AG

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