Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F22%3A10450866" target="_blank" >RIV/00216208:11310/22:10450866 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=2RPo-2uRl4" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=2RPo-2uRl4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celrep.2022.110959" target="_blank" >10.1016/j.celrep.2022.110959</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes

Popis výsledku v původním jazyce

MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8(+) T cells. To understand these affinity differences, human MHC-E (HLA-E)-VL9 versus pathogen-derived peptide structures are compared. Small-angle X-ray scatter (SAXS) measures biophysical parameters in solution, allowing comparison with crystal structures. For HLA-E-VL9, there is concordance between SAXS and crystal parameters. In contrast, HLA-E-bound pathogen-derived peptides produce larger SAXS dimensions that reduce to their crystallographic dimensions only when excess peptide is supplied. Further crystallographic analysis demonstrates three amino acids, exclusive to MHC-E, that not only position VL9 close to the alpha 2 helix, but also allow non-VL9 peptide binding with re-configuration of a key TCR-interacting alpha 2 region. Thus, non-VL9-bound peptides introduce an alternative peptide-binding motif and surface recognition landscape, providing a likely basis for VL9- and non-VL9-HLA-E immune discrimination.

Název v anglickém jazyce

Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes

Popis výsledku anglicky

MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8(+) T cells. To understand these affinity differences, human MHC-E (HLA-E)-VL9 versus pathogen-derived peptide structures are compared. Small-angle X-ray scatter (SAXS) measures biophysical parameters in solution, allowing comparison with crystal structures. For HLA-E-VL9, there is concordance between SAXS and crystal parameters. In contrast, HLA-E-bound pathogen-derived peptides produce larger SAXS dimensions that reduce to their crystallographic dimensions only when excess peptide is supplied. Further crystallographic analysis demonstrates three amino acids, exclusive to MHC-E, that not only position VL9 close to the alpha 2 helix, but also allow non-VL9 peptide binding with re-configuration of a key TCR-interacting alpha 2 region. Thus, non-VL9-bound peptides introduce an alternative peptide-binding motif and surface recognition landscape, providing a likely basis for VL9- and non-VL9-HLA-E immune discrimination.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/GM21-27204M" target="_blank" >GM21-27204M: Molekulární mechanismy navádění axonu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Reports

ISSN

2211-1247

e-ISSN

2639-1856

Svazek periodika

39

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

20

Strana od-do

110959

Kód UT WoS článku

000820353000004

EID výsledku v databázi Scopus

2-s2.0-85131965684