Science - USA (2020-05-22)

SCIENCE sciencemag.org 22 MAY 2020 • VOL 368 ISSUE 6493 841

ILLUSTRATION: NASA/JPL-CALTECH

However, the structural basis of

lethal hit delivery has remained

unknown. Balint et al. enriched

the synaptic output of CTLs to

investigate the released form of

perforin and granzyme B. They

found that CTLs released per-

forin and granzymes in stable

particles called supramolecular

attack complexes or SMAPs.

The SMAPs were composed of

a core shell structure and were

assembled in the CTL dense

secretory granules before

release. The released SMAPs

showed an innate ability to kill

target cells. —SMH

Science, this issue p. 897

STRUCTURAL BIOLOGY

Transport dependent

on context

Transporter proteins move

substrates across a membrane,

often coupling this activity

to cellular ion concentration

gradients. For neurotransmit-

ter transporters, which reside

in synaptic vesicles that fuse

with the plasma membrane

after an action potential,

transport activity needs to

be regulated so that they do

not pump out neurotransmit-

ters after vesicle fusion. Using

cryo–electron microscopy, Li et

al. determined the structure of

a vesicular glutamate trans-

porter from rat that unveils

some of the distinctive features

that enable it to function

properly in two distinct cellular

environments. An allosteric pH

sensor, proposed to be a glu-

tamate residue, gates binding

of the substrate glutamate and

simultaneously permits binding

and counterflow of chloride

ions. This molecular traffic light

allows for a single ion channel

to behave appropriately in dif-

ferent contexts. —MAF

Science, this issue p. 893

T CELL MEMORY

Stepping down resident

memory lane

The antigen-specific CD8+

T cell response to micro-

bial infection includes the

Edited by Caroline Ash

and Jesse Smith

IN OTHER JOURNALS

IMMUNOGENETICS

HLA genetics and COVID-19

Human leukocyte antigens (HLAs)

are proteins encoded by a diverse

set of human genes in the major

histocompatibility complex. Most

people carry between three and

six different HLA alleles that

show geographically specific

distributions. These proteins are

important for how the immune

system recognizes and mounts

immune defenses against infec-

tion. Nguyen et al. examined how

HLA variation affects the cellular

immune response to peptides

from human-infecting corona-

viruses. The authors found that

HLA-B*46:01 had the fewest pre-

dicted binding sites to the severe

acute respiratory syndrome–

coronavirus 2 (SARS-CoV-2)

virus, and HLA-B*15:03 showed

the greatest capacity to present

highly conserved shared SARS-

CoV-2 peptides to immune cells.

HLA typing may therefore offer

valuable information on how coro-

navirus disease 2019 (COVID-19)

might manifest in an individual

and help to prioritize treatment

options. —LMZ

J. Virol. 10.1128/JVI.00510-20 (2020).

differentiation of a subset of

CD8+ T cells into tissue-resi-

dent memory (TRM) cells that

stop circulating and become

confined within a nonlym-

phoid tissue. Kurd et al. used

single-cell RNA sequencing of

mouse CD8+ T cells at multiple

time points during the first

90 days after viral infection to

characterize how this differen-

tiation process unfolds in the

small intestine and to track the

emergence of heterogeneity

among TRM cells. They found

evidence for TRM cell precursors

in the intestine by 4 days after

infection and identified several

putative regulators of TRM cell

differentiation. The results of

this study provide a valuable

transcriptomic atlas that will

facilitate further investigation

into the immune functions

provided by TRM cells. —AB

Sci. Immunol. 5 , eaaz6894 (2020).

CORONAVIRUS

What happens next?

Four months into the severe

acute respiratory syndrome–

coronavirus 2 (SARS-CoV-2)

outbreak, we still do not know

enough about postrecov-

ery immune protection and

environmental and seasonal

influences on transmission to

predict transmission dynam-

ics accurately. However, we do

know that humans are season-

ally afflicted by other, less

severe coronaviruses. Kissler

et al. used existing data to

build a deterministic model of

multiyear interactions between

existing coronaviruses, with

a focus on the United States,

and used this to project the

potential epidemic dynam-

ics and pressures on critical

care capacity over the next 5

years. The long-term dynam-

ics of SARS-CoV-2 strongly

depends on immune responses

and immune cross-reactions

between the coronaviruses, as

well as the timing of introduc-

tion of the new virus into a

population. One scenario is

that a resurgence in SARS-

CoV-2 could occur as far into

the future as 2025. —CA

Science, this issue p. 860

GLACIERS

Continuity in a gap year

T

he Gravitational Recovery and Climate Experiment

(GRACE) and GRACE Follow-On (GRACE-FO) satellite

missions have provided measurements of how much

mass has been lost from the glaciers of the world since

GRACE began operation in 2002. However, GRACE

ended in 2017 and GRACE-FO was not launched until 2018,

creating a data gap of 1.5 years. Is there an offset of their

records? Ciracì et al. report that there is not. Using an

independent dataset, they show that there is continuity in

the satellite mass balance record. This is important because

these glaciers, even though they contain far less mass than

the Greenland or Antarctic ice sheets, were the biggest

contributor to sea-level rise over the 20th century. —HJS

Geophys. Res. Lett. 47 , e2019GL086926 (2020).

Illustration of one of the

twin Gravity Recovery and

Climate Experiment Follow-On

(GRACE-FO) satellites

Published by AAAS