Journal article

Identification of Native and Posttranslationally Modified HLA-B*57:01-Restricted HIV Envelope Derived Epitopes Using Immunoproteomics

Sri H Ramarathinam, Stephanie Gras, Sheilajen Alcantara, Amanda WS Yeung, Nicole A Mifsud, Secondo Sonza, Patricia T Illing, Elias N Glaros, Robert J Center, Shane R Thomas, Stephen J Kent, Nicola Ternette, Damian FJ Purcell, Jamie Rossjohn, Anthony W Purcell

Proteomics | Wiley | Published : 2018

Abstract

The recognition of pathogen‐derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the ER. These peptide‐HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T‐cells leading to the eradication of the infected cell. Here, naturally presented HLA‐B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv) are identified. HIVenv peptides are present at a very small percentage of the overall HLA‐B*57:01 peptidome (<0.1%) and both native and posttranslationally modified..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by Australian Research Council (ARC)


Awarded by NHMRC Senior Research Fellowship


Awarded by NHMRC Early Career Fellowship


Funding Acknowledgements

The authors thank the following funding sources for supporting this work: Australian National Health and Medical Research Council (NHMRC) project grants (APP1085018, APP1084283, APP1129320, and APP1052979); Australian Research Council (ARC) project grant (DP150104503); A.W.P. is supported by a NHMRC Senior Research Fellowship (APP1044215), J.R. is supported by an ARC Laureate Fellowship; S.G. is supported by a Monash Senior Research Fellowship. S.R. was supported by an Australian Postgraduate Award. P.I. is supported by a NHMRC Early Career Fellowship (1072159). The authors would like to thank Dr. David van Bockel and Dr. Anthony Kelleher at the Kirby Institute, UNSW, for HLA-B*57:01-KF11 monomers for HLA tetramer preparation and Lyudmila Kostenko and James McCluskey for the 3E/12 antibody. The authors thank all the study participants and Ms. Julie Silvers and Helen Kent for assistance with recruitment.