Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity
Name
elife-58128-v1.pdf
Description
Published version
Size
3.61 MB
Format
Adobe PDF
Checksum (MD5)
b4555090dd2d4f4205a1cff93b3b7ee8
Author(s)
Mendoza, Juan L
Fischer, Suzanne
Gee, Marvin H
Lam, Lilian H
Brackenridge, Simon
Powrie, Fiona M
Birnbaum, Michael
McMichael, Andrew J
Garcia, K Christopher
Gillespie, Geraldine M
Date Issued
2020
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Version
Final published version
Abstract
© Mendoza et al. T cell cross-reactivity ensures that diverse pathogen-derived epitopes encountered during a lifetime are recognized by the available TCR repertoire. A feature of cross-reactivity where previous exposure to one microbe can alter immunity to subsequent, non-related pathogens has been mainly explored for viruses. Yet cross-reactivity to additional microbes is important to consider, especially in HIV infection where gut-intestinal barrier dysfunction could facilitate T cell exposure to commensal/pathogenic microbes. Here we evaluated the cross-reactivity of a ‘public’, HIV-specific, CD8 T cell-derived TCR (AGA1 TCR) using MHC class I yeast display technology. Via screening of MHC-restricted libraries comprising ~2☓108 sequence-diverse peptides, AGA1 TCR specificity was mapped to a central peptide di-motif. Using the top TCR-enriched library peptides to probe the non-redundant protein database, bacterial peptides that elicited functional responses by AGA1-expressing T cells were identified. The possibility that in context-specific settings, MHC class I proteins presenting microbial peptides influence virus-specific T cell populations in vivo is discussed.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/ELIFE.58128
