Neuromuscular-skeletal constraints on the acquisition of skill in a discrete torque production task

The organisation of the human neuromuscular-skeletal system allows an extremely wide variety of actions to be performed, often with great dexterity. Adaptations associated with skill acquisition occur at all levels of the neuromuscular-skeletal system although all neural adaptations are inevitably constrained by the organisation of the actuating apparatus (muscles and bones). We quantified the extent to which skill acquisition in an isometric task set is influenced by the mechanical properties of the muscles used to produce the required actions. Initial performance was greatly dependent upon the specific combination of torques required in each variant of the experimental task. Five consecutive days of practice improved the performance to a similar degree across eight actions despite differences in the torques required about the elbow and forearm. The proportional improvement in performance was also similar when the actions were performed at either 20 or 40% of participants' maximum voluntary torque capacity. The skill acquired during practice was successfully extrapolated to variants of the task requiring more torque than that required during practice. We conclude that while the extent to which skill can be acquired in isometric actions is independent of the specific combination of joint torques required for target acquisition, the nature of the kinetic adaptations leading to the performance improvement in isometric actions is influenced by the neural and mechanical properties of the actuating muscles.

TCR{alpha} Genes Direct MHC Restriction in the Potent Human T Cell Response to a Class I-Bound Viral Epitope

The underlying generic properties of {alpha}β TCRs that control MHC restriction remain largely unresolved. To investigate MHC restriction, we have examined the CTL response to a viral epitope that binds promiscuously to two human leukocyte Ags (HLAs) that differ by a single amino acid at position 156. Individuals expressing either HLA-B*3501 (156Leucine) or HLA-B*3508 (156Arginine) showed a potent CTL response to the 407HPVGEADYFEY417 epitope from EBV. Interestingly, the response was characterized by highly restricted TCR β-chain usage in both HLA-B*3501+ and HLA-B*3508+ individuals; however, this conserved TRBV9+ β-chain was associated with distinct TCR {alpha}-chains depending upon the HLA-B*35 allele expressed by the virus-exposed host. Functional assays confirmed that TCR {alpha}-chain usage determined the HLA restriction of the CTLs. Structural studies revealed significant differences in the mobility of the peptide when bound to HLA-B*3501 or HLA-B*3508. In HLA-B*3501, the bulged section of the peptide was disordered, whereas in HLA-B*3508 the bulged epitope adopted an ordered conformation. Collectively, these data demonstrate not only that mobile MHC-bound peptides can be highly immunogenic but can also stimulate an extremely biased TCR repertoire. In addition, TCR {alpha}-chain usage is shown to play a critical role in controlling MHC restriction between closely related allomorphs.