Antigen Processing in the Endoplasmic Reticulum Is Monitored by Semi-Invariant {alpha}{beta} TCRs Specific for a Conserved Peptide-Qa-1b MHC Class Ib Ligand [INFECTIOUS DISEASE AND HOST RESPONSE]

Ag processing in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP) is central to presentation of a normal peptide–MHC class I (MHC I) repertoire. Alternations in ERAAP function cause dramatic changes in the MHC I–presented peptides, which elicit potent immune responses. An unusual subset of CD8⁺ T cells monitor normal Ag processing by responding to a highly conserved FL9 peptide that is presented by Qa-1^b, a nonclassical MHC Ib molecule (QFL) in ERAAP-deficient cells. To understand the structural basis for recognition of the conserved ligand, we analyzed the αβ TCRs of QFL-specific T cells. Individual cells in normal wild-type and TCRβ-transgenic mice were assessed for QFL-specific TCR α- and β-chains. The QFL-specific cells expressed a predominant semi-invariant TCR generated by DNA rearrangement of TRAV9d-3–TRAJ21 α-chain and TRBV5–TRBD1–TRBJ2-7 β-chain gene segments. Furthermore, the CDR3 regions of the α- as well as β-chains were required for QFL ligand recognition. Thus, the αβ TCRs used to recognize the peptide–Qa-1 ligand presented by ERAAP-deficient cells are semi-invariant and likely reflect a conserved mechanism for monitoring the fidelity of Ag processing in the ER.

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