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Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain
The role of two central residues (K68, E69) of the fourth hypervariable loop of the Vα domain (HV4α) in antigen recognition by an MHC class II–restricted T cell receptor (TCR) has been analyzed. The TCR recognizes the NH(2)-terminal peptide of myelin basic protein (Ac1-11, acetylated at NH(2) termin...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1999
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192911/ https://www.ncbi.nlm.nih.gov/pubmed/9927513 |
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author | Thatte, Jayant Qadri, Ayub Radu, Caius Ward, E. Sally |
author_facet | Thatte, Jayant Qadri, Ayub Radu, Caius Ward, E. Sally |
author_sort | Thatte, Jayant |
collection | PubMed |
description | The role of two central residues (K68, E69) of the fourth hypervariable loop of the Vα domain (HV4α) in antigen recognition by an MHC class II–restricted T cell receptor (TCR) has been analyzed. The TCR recognizes the NH(2)-terminal peptide of myelin basic protein (Ac1-11, acetylated at NH(2) terminus) associated with the class II MHC molecule I-A(u). Lysine 68 (K68) and glutamic acid 69 (E69) of HV4α have been mutated both individually and simultaneously to alanine (K68A, E69A). The responsiveness of transfectants bearing wild-type and mutated TCRs to Ac1-11–I-A(u) complexes has been analyzed in the presence and absence of expression of the coreceptor CD4. The data demonstrate that in the absence of CD4 expression, K68 plays a central role in antigen responsiveness. In contrast, the effect of mutating E69 to alanine is less marked. CD4 coexpression can partially compensate for the loss of activity of the K68A mutant transfectants, resulting in responses that, relative to those of the wild-type transfectants, are highly sensitive to anti-CD4 antibody blockade. The observations support models of T cell activation in which both the affinity of the TCR for cognate ligand and the involvement of coreceptors determine the outcome of the T cell–antigen-presenting cell interaction. |
format | Text |
id | pubmed-2192911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21929112008-04-16 Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain Thatte, Jayant Qadri, Ayub Radu, Caius Ward, E. Sally J Exp Med Articles The role of two central residues (K68, E69) of the fourth hypervariable loop of the Vα domain (HV4α) in antigen recognition by an MHC class II–restricted T cell receptor (TCR) has been analyzed. The TCR recognizes the NH(2)-terminal peptide of myelin basic protein (Ac1-11, acetylated at NH(2) terminus) associated with the class II MHC molecule I-A(u). Lysine 68 (K68) and glutamic acid 69 (E69) of HV4α have been mutated both individually and simultaneously to alanine (K68A, E69A). The responsiveness of transfectants bearing wild-type and mutated TCRs to Ac1-11–I-A(u) complexes has been analyzed in the presence and absence of expression of the coreceptor CD4. The data demonstrate that in the absence of CD4 expression, K68 plays a central role in antigen responsiveness. In contrast, the effect of mutating E69 to alanine is less marked. CD4 coexpression can partially compensate for the loss of activity of the K68A mutant transfectants, resulting in responses that, relative to those of the wild-type transfectants, are highly sensitive to anti-CD4 antibody blockade. The observations support models of T cell activation in which both the affinity of the TCR for cognate ligand and the involvement of coreceptors determine the outcome of the T cell–antigen-presenting cell interaction. The Rockefeller University Press 1999-02-01 /pmc/articles/PMC2192911/ /pubmed/9927513 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Thatte, Jayant Qadri, Ayub Radu, Caius Ward, E. Sally Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain |
title | Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain |
title_full | Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain |
title_fullStr | Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain |
title_full_unstemmed | Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain |
title_short | Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II–restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the Vα Domain |
title_sort | molecular requirements for t cell recognition by a major histocompatibility complex class ii–restricted t cell receptor: the involvement of the fourth hypervariable loop of the vα domain |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192911/ https://www.ncbi.nlm.nih.gov/pubmed/9927513 |
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