We describe here the structure of a murine T cell receptor (TCR) Vα2.6Jα38 (TCRAV2S6J38) domain, derived from a T cell hybridoma with specificity for the H-2Dd major histocompatibility complex class I molecule bound to a decamer peptide, P18-I10, from the HIV envelope glycoprotein gp120, determined by X-ray crystallography at 2.5 Å resolution. Unlike other TCR Vα domains that have been studied in isolation, this one does not dimerize in solution at concentrations below 1 mM, and the crystal fails to show dimer contacts that are likely to be physiological. In comparison to other Vα domains, this Vα2.6 shows great similarity in the packing of its core residues, and exhibits the same immunoglobulin-like fold characteristic of other TCR Vα domains. There is good electron density in all three complementarity-determining regions (CDRs), where the differences between this Vα domain and others are most pronounced, in particular in CDR3. Examination of crystal contacts reveals an association of Vα domains distinct from those previously seen. Comparison with other Vα domain structures reveals variability in all loop regions, as well as in the first β strand where placement and configuration of a proline residue at position 6, 7, 8, or 9 affects the backbone structure. The great variation in CDR3 conformations among TCR structures is consistent with an evolving view that CDR3 of TCR plays a plastic role in the interaction of the TCR with the MHC/peptide complex as well as with CDR3 of the paired TCR chain.