title: A role for differential variable gene pairing in creating T cell receptors specific for unique major histocompatibility ligands.
abstract: A limited set of T cell receptor (TCR) variable (V) gene segments are used to create a repertoire of TCRs that recognize all major histocompatibility complex (MHC) ligands within a species. How individual αβTCRs are constructed to specifically recognize a limited set of MHC ligands is unclear. Here we have identified a role for the differential pairing of particular V gene segments in creating TCRs that recognized MHC class II ligands exclusively, or cross-reacted with classical and nonclassical MHC class I ligands. Biophysical and structural experiments indicated that TCR specificity for MHC ligands is not driven by germline-encoded pairwise interactions.Rather, identical TCRβ chains can have altered peptide-MHC (pMHC) binding modes when paired with different TCRα chains. The ability of TCR chain pairing to modify how V region residues interact with pMHC helps to explain how the same V genes are used to create TCRs specific for unique MHC ligands.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Stadinski
authors.forename: Peter
authors.initials: P
authors.lastname: Trenh
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Smith
authors.forename: Bianca
authors.initials: B
authors.lastname: Bautista
authors.forename: Priya G
authors.initials: PG
authors.lastname: Huseby
authors.forename: Guoqi
authors.initials: G
authors.lastname: Li
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Stern
authors.forename: Eric S
authors.initials: ES
authors.lastname: Huseby
mesh_terms: D000818:Animals; D003429:Cross Reactions / Q000276:immunology; D006649:Histocompatibility Antigens / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; D008024:Ligands; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta
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