Eintrag weiter verarbeiten
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accesso...
Gespeichert in:
Zeitschriftentitel: | The Journal of experimental medicine |
---|---|
Personen und Körperschaften: | , , |
In: | The Journal of experimental medicine, 184, 1996, 5, S. 1671-1683 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Rockefeller University Press
|
Schlagwörter: |
author_facet |
Shen, L Potter, T A Kane, K P Shen, L Potter, T A Kane, K P |
---|---|
author |
Shen, L Potter, T A Kane, K P |
spellingShingle |
Shen, L Potter, T A Kane, K P The Journal of experimental medicine Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. Immunology Immunology and Allergy |
author_sort |
shen, l |
spelling |
Shen, L Potter, T A Kane, K P 0022-1007 1540-9538 Rockefeller University Press Immunology Immunology and Allergy http://dx.doi.org/10.1084/jem.184.5.1671 <jats:p>Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227--&gt;Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227--&gt;Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227--&gt;Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.</jats:p> Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. The Journal of experimental medicine |
doi_str_mv |
10.1084/jem.184.5.1671 |
facet_avail |
Online Free |
finc_class_facet |
Medizin |
format |
ElectronicArticle |
fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA4NC9qZW0uMTg0LjUuMTY3MQ |
id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA4NC9qZW0uMTg0LjUuMTY3MQ |
institution |
DE-D275 DE-Bn3 DE-Brt1 DE-D161 DE-Zwi2 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 |
imprint |
Rockefeller University Press, 1996 |
imprint_str_mv |
Rockefeller University Press, 1996 |
issn |
0022-1007 1540-9538 |
issn_str_mv |
0022-1007 1540-9538 |
language |
English |
mega_collection |
Rockefeller University Press (CrossRef) |
match_str |
shen1996glu227gtlyssubstitutionintheacidicloopofmajorhistocompatibilitycomplexclassialpha3domaindistinguisheslowaviditycd8coreceptorandavidityenhancedcd8accessoryfunctions |
publishDateSort |
1996 |
publisher |
Rockefeller University Press |
recordtype |
ai |
record_format |
ai |
series |
The Journal of experimental medicine |
source_id |
49 |
title |
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_unstemmed |
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_full |
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_fullStr |
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_full_unstemmed |
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_short |
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_sort |
glu227-->lys substitution in the acidic loop of major histocompatibility complex class i alpha 3 domain distinguishes low avidity cd8 coreceptor and avidity-enhanced cd8 accessory functions. |
topic |
Immunology Immunology and Allergy |
url |
http://dx.doi.org/10.1084/jem.184.5.1671 |
publishDate |
1996 |
physical |
1671-1683 |
description |
<jats:p>Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227--&gt;Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227--&gt;Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227--&gt;Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.</jats:p> |
container_issue |
5 |
container_start_page |
1671 |
container_title |
The Journal of experimental medicine |
container_volume |
184 |
format_de105 |
Article, E-Article |
format_de14 |
Article, E-Article |
format_de15 |
Article, E-Article |
format_de520 |
Article, E-Article |
format_de540 |
Article, E-Article |
format_dech1 |
Article, E-Article |
format_ded117 |
Article, E-Article |
format_degla1 |
E-Article |
format_del152 |
Buch |
format_del189 |
Article, E-Article |
format_dezi4 |
Article |
format_dezwi2 |
Article, E-Article |
format_finc |
Article, E-Article |
format_nrw |
Article, E-Article |
_version_ |
1792335540088995849 |
geogr_code |
not assigned |
last_indexed |
2024-03-01T14:46:10.817Z |
geogr_code_person |
not assigned |
openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Glu227--%26gt%3BLys+substitution+in+the+acidic+loop+of+major+histocompatibility+complex+class+I+alpha+3+domain+distinguishes+low+avidity+CD8+coreceptor+and+avidity-enhanced+CD8+accessory+functions.&rft.date=1996-11-01&genre=article&issn=1540-9538&volume=184&issue=5&spage=1671&epage=1683&pages=1671-1683&jtitle=The+Journal+of+experimental+medicine&atitle=Glu227--%26gt%3BLys+substitution+in+the+acidic+loop+of+major+histocompatibility+complex+class+I+alpha+3+domain+distinguishes+low+avidity+CD8+coreceptor+and+avidity-enhanced+CD8+accessory+functions.&aulast=Kane&aufirst=K+P&rft_id=info%3Adoi%2F10.1084%2Fjem.184.5.1671&rft.language%5B0%5D=eng |
SOLR | |
_version_ | 1792335540088995849 |
author | Shen, L, Potter, T A, Kane, K P |
author_facet | Shen, L, Potter, T A, Kane, K P, Shen, L, Potter, T A, Kane, K P |
author_sort | shen, l |
container_issue | 5 |
container_start_page | 1671 |
container_title | The Journal of experimental medicine |
container_volume | 184 |
description | <jats:p>Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227--&gt;Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227--&gt;Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227--&gt;Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.</jats:p> |
doi_str_mv | 10.1084/jem.184.5.1671 |
facet_avail | Online, Free |
finc_class_facet | Medizin |
format | ElectronicArticle |
format_de105 | Article, E-Article |
format_de14 | Article, E-Article |
format_de15 | Article, E-Article |
format_de520 | Article, E-Article |
format_de540 | Article, E-Article |
format_dech1 | Article, E-Article |
format_ded117 | Article, E-Article |
format_degla1 | E-Article |
format_del152 | Buch |
format_del189 | Article, E-Article |
format_dezi4 | Article |
format_dezwi2 | Article, E-Article |
format_finc | Article, E-Article |
format_nrw | Article, E-Article |
geogr_code | not assigned |
geogr_code_person | not assigned |
id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA4NC9qZW0uMTg0LjUuMTY3MQ |
imprint | Rockefeller University Press, 1996 |
imprint_str_mv | Rockefeller University Press, 1996 |
institution | DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Zwi2, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
issn | 0022-1007, 1540-9538 |
issn_str_mv | 0022-1007, 1540-9538 |
language | English |
last_indexed | 2024-03-01T14:46:10.817Z |
match_str | shen1996glu227gtlyssubstitutionintheacidicloopofmajorhistocompatibilitycomplexclassialpha3domaindistinguisheslowaviditycd8coreceptorandavidityenhancedcd8accessoryfunctions |
mega_collection | Rockefeller University Press (CrossRef) |
physical | 1671-1683 |
publishDate | 1996 |
publishDateSort | 1996 |
publisher | Rockefeller University Press |
record_format | ai |
recordtype | ai |
series | The Journal of experimental medicine |
source_id | 49 |
spelling | Shen, L Potter, T A Kane, K P 0022-1007 1540-9538 Rockefeller University Press Immunology Immunology and Allergy http://dx.doi.org/10.1084/jem.184.5.1671 <jats:p>Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227--&gt;Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227--&gt;Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227--&gt;Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.</jats:p> Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. The Journal of experimental medicine |
spellingShingle | Shen, L, Potter, T A, Kane, K P, The Journal of experimental medicine, Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions., Immunology, Immunology and Allergy |
title | Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_full | Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_fullStr | Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_full_unstemmed | Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_short | Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
title_sort | glu227-->lys substitution in the acidic loop of major histocompatibility complex class i alpha 3 domain distinguishes low avidity cd8 coreceptor and avidity-enhanced cd8 accessory functions. |
title_unstemmed | Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions. |
topic | Immunology, Immunology and Allergy |
url | http://dx.doi.org/10.1084/jem.184.5.1671 |