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Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells
The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation una...
Formato: | Texto |
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Lenguaje: | English |
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The Rockefeller University Press
1992
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119298/ https://www.ncbi.nlm.nih.gov/pubmed/1613468 |
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collection | PubMed |
description | The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes. |
format | Text |
id | pubmed-2119298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1992 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21192982008-04-16 Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells J Exp Med Articles The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes. The Rockefeller University Press 1992-07-01 /pmc/articles/PMC2119298/ /pubmed/1613468 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 Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells |
title | Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells |
title_full | Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells |
title_fullStr | Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells |
title_full_unstemmed | Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells |
title_short | Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells |
title_sort | requirement for cd8-major histocompatibility complex class i interaction in positive and negative selection of developing t cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119298/ https://www.ncbi.nlm.nih.gov/pubmed/1613468 |