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 α2 helix, but also allow non-VL9 peptide binding with re-configuration of a key TCR-interacting α2 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.

• MeSH
• CD8-pozitivní T-lymfocyty MeSH
• difrakce rentgenového záření MeSH
• konformace proteinů MeSH
• lektinové receptory NK-buněk - podrodina C metabolismus   MeSH
• lidé MeSH
• maloúhlový rozptyl MeSH
• MHC antigeny I. třídy * metabolismus   MeSH
• peptidy metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we report the isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing of HLA-E-VL9-expressing cells by an NKG2A+ NK cell line. Structural analysis reveal that 3H4 acts by preventing CD94/NKG2A docking on HLA-E-VL9. Upon in vitro maturation, an affinity-optimized IgG form of 3H4 showes enhanced NK killing of HLA-E-VL9-expressing cells. HLA-E-VL9-specific IgM antibodies similar in function to 3H4 are also isolated from naïve B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naïve B cell antibody pool have the capacity to enhance NK cell cytotoxicity.

• MeSH
• buňky NK MeSH
• cytotoxicita imunologická * MeSH
• HLA antigeny MeSH
• imunoglobuliny metabolismus   MeSH
• lidé MeSH
• MHC antigeny I. třídy * genetika   MeSH
• myši MeSH
• peptidy metabolismus   MeSH
• proteiny - lokalizační signály MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

T follicular helper (Tfh) cells are fundamental for B cell selection and antibody maturation in germinal centers. Circulating Tfh (cTfh) cells constitute a minor proportion of the CD4+ T cells in peripheral blood, but their clonotypic relationship to Tfh populations resident in lymph nodes and the extent to which they differ from non-Tfh CD4+ cells have been unclear. Using donor-matched blood and tonsil samples, we investigate T cell receptor (TCR) sharing between tonsillar Tfh cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing reveals considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. Furthermore, influenza-specific cTfh cell clones derived from blood can be found in the repertoire of tonsillar Tfh cells. Therefore, human blood samples can be used to gain insight into the specificity of Tfh responses occurring in lymphoid tissues, provided that cTfh subsets are studied.

• MeSH
• buněčné klony cytologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• dárci tkání MeSH
• dospělí MeSH
• folikulární pomocné T-buňky imunologie   MeSH
• hemaglutininové glykoproteiny viru chřipky imunologie   MeSH
• krční mandle imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• počítačová simulace MeSH
• podskupiny lymfocytů imunologie   MeSH
• receptory CXCR3 metabolismus   MeSH
• velikost buňky MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

• Klíčová slova
• Laboratorní technika, Lymfocyty,
• MeSH
• klinické laboratorní techniky MeSH
• lymfocyty MeSH

• MeSH
• genetika člověka MeSH
• geny MHC třídy I MeSH
• geny MHC třídy II MeSH
• HLA-A antigeny MeSH
• imunita MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika
• biologie

• Klíčová slova
• rakovina,

• NLK Obory
• onkologie
• NLK Publikační typ
• publikace WHO

• MeSH
• leukocyty MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• hematologie a transfuzní lékařství

• MeSH
• geny MeSH
• imunologická odpověď na dávku MeSH
• regulace genové exprese MeSH
• Publikační typ
• kongresy MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• alergologie a imunologie
• genetika, lékařská genetika