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Publication Abstract from PubMed

Unconventional HLA class I-restricted CD8(+) T cell epitopes, longer than 10 aa, have been implicated to play a role in human immunity against viruses and cancer. T cell recognition of long peptides, centrally bulging from the HLA cleft, has been described previously. Alternatively, long peptides can contain a linear HLA-bound core peptide, with a N- or C-terminal peptide "tail" extending from the HLA peptide binding groove. The role of such a peptide "tail" in CD8(+) T cell recognition remains unclear. In this study, we identified a 20mer peptide (FLPTPEELGLLGPPRPQVLA [FLP]) derived from the IL-27R subunit alpha gene restricted to HLA-A*02:01, for which we solved the crystal structure and demonstrated a long C-terminal "tail" extension. FLP-specific T cell clones demonstrated various recognition modes, some T cells recognized the FLP core peptide, while for other T cells the peptide tail was essential for recognition. These results demonstrate a crucial role for a C-terminal peptide tail in immunogenicity.

Cutting Edge: Unconventional CD8(+) T Cell Recognition of a Naturally Occurring HLA-A*02:01-Restricted 20mer Epitope.,Meeuwsen MH, Wouters AK, Hagedoorn RS, Kester MGD, Remst DFG, van der Steen DM, de Ru A, van Veelen PA, Rossjohn J, Gras S, Falkenburg JHF, Heemskerk MHM J Immunol. 2022 Apr 15;208(8):1851-1856. doi: 10.4049/jimmunol.2101208. Epub 2022 , Apr 4. PMID:35379743^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.