27EU

Human Leucocyte Antigen HLA-A2 with bound PB1(413-421) peptide

Summary for 27EU

• Entry DOI: 10.2210/pdb27eu/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, PB1(413-421) peptide, ... (5 entities in total)
• Functional Keywords: human leucocyte antigen influenza peptide, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 46850.19

Authors

Petersen, J.,Gras, S.,Rossjohn, J. (deposition date: 2026-05-28, release date: 2026-11-11)

Primary citation

Koutsakos, M.,Crawford, J.C.,Grzelak, L.,Rizzetto, S.,Nguyen, A.T.,Chaurasia, P.,Petersen, J.,Rowntree, L.C.,Allen, E.K.,Tong, S.Y.C.,Cheng, A.C.,Kotsimbos, T.C.,Luciani, F.,Rossjohn, J.,Gras, S.,Thomas, P.G.,Nguyen, T.H.O.,Kedzierska, K.
TCR alpha beta repertoire plasticity defines universal CD8+ T cell responses directed at influenza-specific HLA-A*02:01-PB1413-421 epitope.
J Immunol., 215:-, 2026

PubMed Abstract: HLA-A*02:01-restricted PB1413+CD8+ T cells provide the broadest reported cross-reactive immunity against influenza A, B, and C viruses. Here, we investigated T cell receptor (TCR) clonotypic signatures within these universal A2/PB1413+CD8+ T cell pools, compared with immunodominant influenza A-specific M158+CD8+ T cells and codominant influenza B-specific A2/HA543+CD8+ memory T cells. Using single-cell reverse transcriptase polymerase chain reaction and RNA sequencing methodologies, we defined TCRαβ repertoire composition and diversity. Our study shows that CD8+ T cells responding to these 3 epitopes differ in magnitude and TCRαβ repertoires in terms of gene usage and sharing, underpinned by specific TCR and structural features for each pMHC-I specificity. Our data demonstrated that the A2/PB1413+CD8+ TCRαβ repertoire encompassed diverse gene segment usage within both TCRα and TCRβ chains. These were, however, greatly variable across HLA-A2*02:01-expressing individuals and lacked any shared features within TRAV, TRBV, TRBJ, and TRAJ gene segments. This A2/PB1413+CD8+ TCRαβ diversity stemmed from the low probability of recombination attributed to a large number of N-insertions in the TCRβ chain. PB1413+CD8+ T cells also displayed remarkable plasticity in recognition of the A2/PB1413 epitope depicted by versatile CD8+ T cell recognition patterns of the universal A2/PB1413 epitope across HLA-A*02:01-expressing individuals. Conversely, TCRαβ repertoires within A2/BHA543+CD8+ and M158+CD8+ T cells displayed common TRAV, TRBV, TRBJ, and TRAJ gene segments, shared across HLA-A*02:01-expressing individuals and recognizing key residues within A2/BHA543 and A2/M158 epitopes. Overall, our data showed a great level of TCRαβ gene usage diversity within universal A2/PB1413+CD8+ T cells, indicating that the TCRαβ clonal plasticity defines universal immunity toward human influenza viruses.

PubMed: 42886732
DOI: 10.1093/jimmun/vkag270

Experimental method

X-RAY DIFFRACTION (2.32 Å)