| 3 | TCR-pMHC:Envisioning the specialized dynamics of the target 5-component complex显示文摘The mechanosensor theory of TCR function holds theα/βcomponent of the T-cell antigen receptor complex ultimately responsible for adaptive immunity[1,2,3].T-cell motility is envisioned to provide a force necessary to slow TCR dynamics as it sits on the pMHC ligand of an antigen presenting cell[1],which theoretically allows the TCR to discriminate different pMHC structures,principally by the so-called catch bonds(mostly H-bonds)at the interfaces of the 5-component complex(i.e.,TCRα/TCRβ/peptide/MHC-IIα(or,MHC-heavy-chain)/MHC-IIβ(or MHC-light-chain)[1,2,3,4]. | Joseph S.Murray | 2022 | Cellular & Molecular Immunology2022，19，6： | 0 |
| 4 | TCR-pMHC: may the force be of you?显示文摘Theα/βcomponent of the T-cell antigen receptor(TCR)is a transmembrane heterodimer containing genetically variable(V)domains and constant domains within each polypeptide chain.1 The Vαand Vβdomains bind with a clonally unique(clonotypic)interface angle,2 and the complementary determining regions(CDR1,CDR2,and CDR3)manifest as‘loops’between anti-parallelβ-strands of the overall sandwich ofβ-sheets with a central disulfide bond.As with immunoglobulins,the CDR1 and CDR2 loops are encoded in the germline via the particular V-region DNA segment involved in the RAG1/RAG2 recombination mechanism responsible for somatic construction,together with the D-and/or J-segment,of the third loop,CDR3.1,3 As shown by multiple solved X-ray crystallography structures,the CDRs contain the closest amino acid(a.a.)contacts with the peptide(p)plus the major histocompatibility complex(MHC)protein(together abbrev.,pMHC)composite ligand.After rigorous selection in the thymus for only those TCRs that should function properly in the particular individual after birth(MHC restriction),4 T cells function clonally as well,i.e.,different T-cell clones display differential responses to not only different pMHC ligands but also perhaps more importantly,to the same pMHC ligands.5,6 A long-standing question is how(not whether)TCR V-domain binding to pMHC is ultimately responsible for such vast biological outcomes as protection vs.susceptibility to infectious diseases,atopy,the onset of autoimmune diseases,and the success of various types of transplantation. | Joseph S.Murray | 2021 | Cellular & Molecular Immunology2021，18，7： | 0 |
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