24st

Crystal Structure of the cross-restricted 14D7 TCR and HLA-B*81:01 bound to HIV-1 Gag TL9 peptide

spinqualitylabelsall models 24st, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 24st is a 5 chain structure with sequence from Homo sapiens and Human immunodeficiency virus type 1 (WMJ2 ISOLATE). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease B2MG_HUMAN Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation. Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis. Function B2MG_HUMAN Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed Dual-reactive T cell receptors (TCRs) that recognize the HIV-1 Gag TL9 epitope presented by both HLA-B*81:01 and HLA-B*42:01 are associated with improved immune control. However, whether such TCRs rely on a single universal recognition blueprint or adopt distinct structural solutions remains unclear. Here, we characterize 14D7, an additional dual-reactive TL9-specific TCR, and compare its structural features with those of the previously reported T18A clonotype. The 14D7-HLA-B*81:01-TL9 structure reveals a conserved non-canonical recognition framework shared with T18A: in both TCRs, CDR3beta primarily engages the HLA alpha2 helix rather than the peptide, while CDR2beta compensates via critical peptide contacts. However, 14D7 adopts a distinct CDR3 loop conformation, likely reflecting differences in V/J gene usage and junctional rearrangement, demonstrating that dual-reactive TCRs can achieve cross-reactivity through related but non-identical molecular solutions. AlphaFold 3 modeling further suggests that, like T18A, 14D7 actively remodels the TL9 conformation in the HLA-B*42:01 context toward a state resembling that observed in the HLA-B*81:01-bound complex. Surface plasmon resonance analysis revealed differential affinity profiles across HLA backgrounds, with greater tolerance to common escape variants in the HLA-B*81:01 context. Structural comparison further suggests that polymorphic HLA residues, particularly at positions 143 and 163, reshape the peptide- and TCR-facing interaction network and thereby influence tolerance to epitope variation. Together, these findings show that dual-reactive TCRs operate within a conserved non-canonical recognition framework while retaining flexibility at the level of CDR3 loop configuration, providing a refined structural basis for HIV-specific cross-reactive T cell immunity. Conserved non-canonical recognition with distinct structural solutions underlies dual-HLA recognition of HIV-1 Gag TL9.,Meng J, Lei J, Wei Q, Wei P Int J Biol Macromol. 2026 Jun;369:152866. doi: 10.1016/j.ijbiomac.2026.152866. , Epub 2026 Jun 1. PMID:42229649 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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