Allelic variation in class I HLA determines CD8 T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2.

Effective presentation of antigens by human leukocyte antigen (HLA) class I molecules to CD8 T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multiomic technology to generate a unified ex vivo characterization of the CD8 T cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across four major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCRα/β sequence diversity, and the utilization of pre-existing SARS-CoV-2-reactive memory T cell pools.

Generalization of learned responses in the mormyrid electrosensory lobe.

Appropriate generalization of learned responses to new situations is vital for adaptive behavior. We provide a circuit-level account of generalization in the electrosensory lobe (ELL) of weakly electric mormyrid fish. Much is already known in this system about a form of learning in which motor corollary discharge signals cancel responses to the uninformative input evoked by the fish's own electric pulses.

A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds.

The dorsal cochlear nucleus (DCN) integrates auditory nerve input with a diverse array of sensory and motor signals processed in circuitry similar to that of the cerebellum. Yet how the DCN contributes to early auditory processing has been a longstanding puzzle. Using electrophysiological recordings in mice during licking behavior, we show that DCN neurons are largely unaffected by self-generated sounds while remaining sensitive to external acoustic stimuli.

The Timing Is Right for Cerebellar Learning.

In this issue of Neuron, Suvrathan et al. (2016) provide a striking demonstration of a plasticity rule with temporal properties precisely matched to the computational requirements of behavioral learning and suggest major revisions to the rules for synaptic plasticity in the cerebellum.