Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(4)
Published: Jan. 17, 2023
Adaptive
immunity
is
driven
by
specific
binding
of
hypervariable
receptors
to
diverse
molecular
targets.
The
sequence
diversity
and
targets
are
both
individually
known
but
because
multiple
can
recognize
the
same
target,
a
measure
effective
“functional”
human
immune
system
has
remained
elusive.
Here,
we
show
that
near-coincidences
within
T
cell
bind
epitopes
provide
new
window
into
this
problem
allow
quantification
how
probability
covaries
with
sequence.
We
find
near-coincidence
statistics
epitope-specific
repertoires
imply
degeneracy
amino
acid
changes
in
receptor
consistent
across
disparate
experiments.
Paired
data
on
chains
heterodimeric
particularly
revealing
since
simultaneous
rare
they
be
exploited
estimate
number
epitope
responses
created
memory
compartment.
In
addition,
paired-chain
coincidences
strongly
suppressed
donors
different
leukocyte
antigens,
evidence
for
central
role
antigen-driven
selection
making
paired
chain
public.
These
results
demonstrate
power
coincidence
analysis
reveal
determinants
repertoires.
Immunological Reviews,
Journal Year:
2022,
Volume and Issue:
310(1), P. 27 - 46
Published: June 22, 2022
Immunological
memory
is
the
basis
of
protective
immunity
provided
by
vaccines
and
previous
infections.
can
develop
from
multiple
branches
adaptive
immune
system,
including
CD4
T
cells,
CD8
B
long-lasting
antibody
responses.
Extraordinary
progress
has
been
made
in
understanding
to
SARS-CoV-2
infection
COVID-19
vaccines,
addressing
development;
quantitative
qualitative
features
different
cellular
anatomical
compartments;
durability
each
component
antibodies.
Given
sophistication
measurements;
size
human
studies;
use
longitudinal
samples
cross-sectional
head-to-head
comparisons
between
or
for
1
year
already
supersedes
that
any
other
acute
infectious
disease.
This
knowledge
may
help
inform
public
policies
regarding
as
well
scientific
development
future
against
diseases.
Nature,
Journal Year:
2023,
Volume and Issue:
620(7972), P. 128 - 136
Published: July 19, 2023
Abstract
Studies
have
demonstrated
that
at
least
20%
of
individuals
infected
with
SARS-CoV-2
remain
asymptomatic
1–4
.
Although
most
global
efforts
focused
on
severe
illness
in
COVID-19,
examining
infection
provides
a
unique
opportunity
to
consider
early
immunological
features
promote
rapid
viral
clearance.
Here,
postulating
variation
the
human
leukocyte
antigen
(
HLA
)
loci
may
underly
processes
mediating
infection,
we
enrolled
29,947
individuals,
for
whom
high-resolution
genotyping
data
were
available,
smartphone-based
study
designed
track
COVID-19
symptoms
and
outcomes.
Our
discovery
cohort
n
=
1,428)
comprised
unvaccinated
who
reported
positive
test
result
SARS-CoV-2.
We
tested
association
five
disease
course
identified
strong
between
HLA-B*15:01
observed
two
independent
cohorts.
Suggesting
this
genetic
is
due
pre-existing
T
cell
immunity,
show
cells
from
pre-pandemic
samples
carrying
reactive
immunodominant
S-derived
peptide
NQKLIANQF.
The
majority
displayed
memory
phenotype,
highly
polyfunctional
cross-reactive
derived
seasonal
coronaviruses.
crystal
structure
HLA-B*15:01–peptide
complexes
demonstrates
peptides
NQKLIANQF
NQKLIANAF
(from
OC43-CoV
HKU1-CoV)
share
similar
ability
be
stabilized
presented
by
HLA-B*15:01.
Finally,
structural
similarity
underpins
cross-reactivity
high-affinity
public
receptors,
providing
molecular
basis
-mediated
immunity.
Annual Review of Immunology,
Journal Year:
2023,
Volume and Issue:
41(1), P. 343 - 373
Published: Feb. 8, 2023
A
large
body
of
evidence
generated
in
the
last
two
and
a
half
years
addresses
roles
T
cells
SARS-CoV-2
infection
following
vaccination.
Infection
or
vaccination
induces
multi-epitope
CD4
CD8
cell
responses
with
polyfunctionality.
Early
have
been
associated
mild
COVID-19
outcomes.
In
concert
animal
model
data,
these
results
suggest
that
while
antibody
are
key
to
prevent
infection,
may
also
play
valuable
reducing
disease
severity
controlling
infection.
memory
after
is
sustained
for
at
least
six
months.
While
neutralizing
impacted
by
variants,
most
preserved.
This
review
highlights
extensive
progress
made,
data
knowledge
gaps
remain,
our
understanding
vaccines.
The Journal of Experimental Medicine,
Journal Year:
2022,
Volume and Issue:
219(10)
Published: Aug. 16, 2022
Rapid
recognition
of
SARS-CoV-2-infected
cells
by
resident
T
in
the
upper
airway
might
provide
an
important
layer
protection
against
COVID-19.
Whether
parenteral
SARS-CoV-2
vaccination
or
infection
induces
nasal-resident
specific
for
distinct
proteins
is
unknown.
We
isolated
from
nasal
mucosa
COVID-19
vaccinees
who
either
experienced
after
(n
=
34)
not
16)
and
analyzed
their
phenotype,
specificity,
function,
persistence.
Nasal-resident
SARS-CoV-2-specific
CD8+
CD4+
were
detected
almost
exclusively
breakthrough
infection.
Importantly,
Spike-specific
primed
did
suppress
induction
other
proteins.
The
cell
responses
persisted
≥140
d,
with
minimal
sign
waning.
These
data
highlight
importance
viral
challenge
formation
antiviral
immunity
at
site
primary
further
define
immunological
features
hybrid
immunity.
The
regulatory
and
effector
functions
of
T
cells
are
initiated
by
the
binding
their
cell-surface
cell
receptor
(TCR)
to
peptides
presented
major
histocompatibility
complex
(MHC)
proteins
on
other
cells.
specificity
TCR:peptide-MHC
interactions,
thus,
underlies
nearly
all
adaptive
immune
responses.
Despite
intense
interest,
generalizable
predictive
models
remain
out
reach;
two
key
barriers
diversity
TCR
recognition
modes
paucity
training
data.
Inspired
recent
breakthroughs
in
protein
structure
prediction
achieved
deep
neural
networks,
we
evaluated
structural
modeling
as
a
potential
avenue
for
epitope
specificity.
We
show
that
specialized
version
network
predictor
AlphaFold
can
generate
interactions
be
used
discriminate
correct
from
incorrect
peptide
epitopes
with
substantial
accuracy.
Although
much
work
remains
done
these
predictions
have
widespread
practical
utility,
optimistic
learning-based
represents
path
interaction
