Crystal structure of a T cell receptor V alpha 11 (AV11S5) domain: New canonical forms for the first and second complementarity determining regions

We describe the X-ray crystallographic structure of a murine T cell recepto r (TCR) V alpha domain ("V alpha 85.33 "; AV11S5-AJ17) to 1.85 Angstrom res olution. The V alpha 85.33 domain is derived from a TCR that recognizes a t ype II collagen peptide associated with the murine major histocompatibility complex (MHC) class II molecule, I-A(q). V alpha 85.33 packs as a V alpha -V alpha homodimer with a highly symmetric monomer-monomer interface. The f irst and second complementarity determining regions (CDR1 and CDR2) of this Ver are shorter than the CDRs corresponding to the majority of other V alp ha gene families, and three-dimensional structures of CDRs of these lengths have not been described previously. The CDR1 and CDR2 therefore represent new canonical forms that could serve as templates for AV11 family members. CDR3 of the V alpha 85.33 domain is highly flexible and this is consistent with plasticity of this region of the TCR. The fourth hypervariable loop (H V4 alpha) of AV11 and AV10 family members is one residue longer than that o f other HV4 alpha regions and shows a high degree of flexibility. The incre ase in length results in a distinct disposition of the conserved residue Ly s68, which has been shown in other studies to play a role in antigen recogn ition. The X-ray structure of V alpha 85.33 extends the database of canonic al forms for CDR1 and CDR2, and has implications for antigen recognition by TCRs that contain related Vex domains. (C) 2001 Academic Press.