Antigen Processing in the Endoplasmic Reticulum Is Monitored by Semi-Invariant ab TCRs Specific for a Conserved Peptide-Qa-1(b) MHC Class Ib Ligand

作者：Guan, Jian; Yang, Soo Jung; Gonzalez, Federico; Yin, Yuxin^*; Shastri, Nilabh^*

来源：The Journal of Immunology, 2017, 198(5): 2017-2027.

DOI：10.4049/jimmunol.1600764

• T-CELL ANTIGEN
• RECEPTOR-ALPHA-CHAIN
• POSITIVE SELECTION
• IN-VIVO
• RECOGNITION
• MOLECULES
• PEPTIDES
• ERAP1
• EXPRESSION
• AMINOPEPTIDASE

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 ab TCRs of QFL-specific T cells. Individual cells in normal wild-type and TCR beta-transgenic mice were assessed for QFL-specific TCR alpha-and beta-chains. The QFL-specific cells expressed a predominant semi-invariant TCR generated by DNA rearrangement of TRAV9d-3-TRAJ21 alpha-chain and TRBV5-TRBD1-TRBJ2-7 b-chain gene segments. Furthermore, the CDR3 regions of the alpha-as well as beta-chains were required for QFL ligand recognition. Thus, the ab 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.

• 出版日期2017-3-1
• 单位北京大学