TCRpair: prediction of functional pairing between HLA-A*02:01-restricted T cell receptor α and β chains

Author(s):  
Anja Mösch ◽  
Dmitrij Frishman

Abstract Summary The ability of a T cell to recognize foreign peptides is defined by a single α and a single β hypervariable complementarity determining region (CDR3), which together form the T cell receptor (TCR) heterodimer. In ∼30%-35% of T cells, two α chains are expressed at the mRNA level but only one α chain is part of the functional TCR. This effect can also be observed for β chains, although it is less common. The identification of functional α/β chain pairs is instrumental in high-throughput characterization of therapeutic TCRs. TCRpair is the first method that predicts whether an α and β chain pair forms a functional, HLA-A*02:01 specific TCR without requiring the sequence of a recognized peptide. By taking additional amino acids flanking the CDR3 regions into account, TCRpair achieves an AUC of 0.71. Availability TCRpair is implemented in Python using TensorFlow 2.0 and is freely available at https://www.github.com/amoesch/TCRpair Supplementary information Supplementary data are available at Bioinformatics online.

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 571
Author(s):  
Giovanna Linguiti ◽  
Sofia Kossida ◽  
Ciro Leonardo Pierri ◽  
Joumana Jabado-Michaloud ◽  
Geraldine Folch ◽  
...  

The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary, and expression study of T. truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3′ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi-sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the complementarity-determining region according to IMGT numbering (CDR-IMGT) of the dolphin variable V-alpha and beta domains were identified. According to comparative modelization, the atom pair contact sites analysis between the human MH1 grove (G) domains and the T cell receptor (TR) V domains confirms conservation of the structure of the dolphin TR/pMH.


2020 ◽  
Vol 295 (42) ◽  
pp. 14445-14457 ◽  
Author(s):  
Wael Awad ◽  
Erin W. Meermeier ◽  
Maria L. Sandoval-Romero ◽  
Jérôme Le Nours ◽  
Aneta H. Worley ◽  
...  

MR1 presents vitamin B–related metabolites to mucosal associated invariant T (MAIT) cells, which are characterized, in part, by the TRAV1-2+ αβ T cell receptor (TCR). In addition, a more diverse TRAV1-2− MR1-restricted T cell repertoire exists that can possess altered specificity for MR1 antigens. However, the molecular basis of how such TRAV1-2− TCRs interact with MR1–antigen complexes remains unclear. Here, we describe how a TRAV12-2+ TCR (termed D462-E4) recognizes an MR1–antigen complex. We report the crystal structures of the unliganded D462-E4 TCR and its complex with MR1 presenting the riboflavin-based antigen 5-OP-RU. Here, the TRBV29-1 β-chain of the D462-E4 TCR binds over the F′-pocket of MR1, whereby the complementarity-determining region (CDR) 3β loop surrounded and projected into the F′-pocket. Nevertheless, the CDR3β loop anchored proximal to the MR1 A′-pocket and mediated direct contact with the 5-OP-RU antigen. The D462-E4 TCR footprint on MR1 contrasted that of the TRAV1-2+ and TRAV36+ TCRs' docking topologies on MR1. Accordingly, diverse MR1-restricted T cell repertoire reveals differential docking modalities on MR1, thus providing greater scope for differing antigen specificities.


1988 ◽  
Vol 12 (3) ◽  
pp. 227-232 ◽  
Author(s):  
Masayoshi Minegishi ◽  
Shigeru Tsuchiya ◽  
Naoko Minegishi ◽  
Osamu Yoshie ◽  
Masataka Nakamura ◽  
...  

1995 ◽  
Vol 270 (43) ◽  
pp. 25819-25826 ◽  
Author(s):  
Bryan K. Cho ◽  
Beth A. Schodin ◽  
David M. Kranz

2010 ◽  
Vol 286 (6) ◽  
pp. 4871-4881 ◽  
Author(s):  
A. K. M. Nur-ur Rahman ◽  
Daniel A. Bonsor ◽  
Christine A. Herfst ◽  
Fraser Pollard ◽  
Michael Peirce ◽  
...  

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