Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep;21(17-18):e2100142.
doi: 10.1002/pmic.202100142. Epub 2021 Aug 1.

Direct identification of HLA-presented CD8 T cell epitopes from transmitted founder HIV-1 variants

Affiliations

Direct identification of HLA-presented CD8 T cell epitopes from transmitted founder HIV-1 variants

Jonathan Hare et al. Proteomics. 2021 Sep.

Abstract

Cytotoxic T lymphocytes (CTLs) are a critical arm of the immune response to viral infections. The activation and expansion of antigen specific CTL requires recognition of peptide antigens presented on class I major histocompatibility complex molecules (MHC-1) of infected cells. Methods to identify presented peptide antigens that do not rely on the pre-existence of antigen specific CTL are critical to the development of new vaccines. We infected activated CD4+ T cells with two HIV-1 transmitted founder (TF) isolates and used high-resolution mass spectrometry (MS) to identify HIV peptides bound on MHC-1. Using this approach, we identified 14 MHC-1 bound peptides from across the two TF isolates. Assessment of predicted binding thresholds revealed good association of the identified peptides to the shared HLA alleles between the HIV+ donors and the naïve PBMC sample with three peptides identified through peptide sequencing inducing a CD8 T-cell response (p < 0.05). Direct infection of naïve CD4 cells by HIV TF isolates and sequencing of MHC-I presented peptides by HPLC-MS/MS enables identification of novel peptides that may be missed by alternative epitope mapping strategies and can provide valuable insight in to the first peptides presented by an HIV-infected CD4 cell in the first few days post infection.

Keywords: biomedicine; immunoproteomics; infectious diseases; mass spectrometry-LC-MS/MS; technology.

PubMed Disclaimer

Similar articles

Cited by

References

REFERENCES

    1. Appay, V., Papagno, L., Spina, C. A., Hansasuta, P., King, A., Jones, L., Ogg, G. S., Little, S., Mcmichael, A. J., Richman, D. D., & Rowland-Jones, S. L. (2002). Dynamics of T cell responses in HIV infection. Journal of Immunology, 168(7), 3660-3666.
    1. Goonetilleke, N., Liu, M. K. P., Salazar-Gonzalez, J. F., Ferrari, G., Giorgi, E., Ganusov, V. V., Keele, B. F., Learn, G. H., Turnbull, E. L., Salazar, M. G., Weinhold, K. J., Moore, S., Letvin, N., Haynes, B. F., Cohen, M. S., Hraber, P., Bhattacharya, T., Borrow, P., Perelson, A. S., … Mcmichael, A. J. (2009). The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. Journal of Experimental Medicine, 206(6), 1253-1272. https://doi.org/10.1084/jem.20090365
    1. Bosinger S. E., Jochems S. P., Folkner K. A., Hayes T. L., Klatt N. R., & Silvestri G. (2013). Transcriptional profiling of experimental CD8(+) lymphocyte depletion in rhesus macaques infected with simian immunodeficiency virus SIVmac239. Journal of Virology, 87(1), 433-443. https://doi.org/10.1128/jvi.01746-12
    1. Pandrea, I., Gaufin, T., Gautam, R., Kristoff, J., Mandell, D., Montefiori, D., Keele, B. F., Ribeiro, R. M., Veazey, R. S., & Apetrei, C. (2011). Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion. PLoS Pathogens, 7(8), e1002170. https://doi.org/10.1371/journal.ppat.1002170
    1. Arunachalam, P. S., Charles, T. P., Joag, V., Bollimpelli, V. S., Scott, M. K. D., Wimmers, F., Burton, S. L., Labranche, C. C., Petitdemange, C., Gangadhara, S., Styles, T. M., Quarnstrom, C. F., Walter, K. A., Ketas, T. J., Legere, T., Jagadeesh Reddy, P. B., Kasturi, S. P., Tsai, A., Yeung, B. Z., … Pulendran, B. (2020). T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers. Nature Medicine, 26(6), 932-940. https://doi.org/10.1038/s41591-020-0858-8

Publication types

Substances

LinkOut - more resources