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Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry
The T cell receptor (TCR), from a xeno-reactive murine cytotoxic T lymphocyte clone AHIII12.2, recognizes murine H-2D(b) complexed with peptide p1027 (FAPGVFPYM), as well as human HLA-A2.1 complexed with peptide p1049 (ALWGFFPVL). A commonly proposed model (the molecular mimicry model) used to expla...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1999
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192988/ https://www.ncbi.nlm.nih.gov/pubmed/9892618 |
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author | Zhao, Rui Loftus, Douglas J. Appella, Ettore Collins, Edward J. |
author_facet | Zhao, Rui Loftus, Douglas J. Appella, Ettore Collins, Edward J. |
author_sort | Zhao, Rui |
collection | PubMed |
description | The T cell receptor (TCR), from a xeno-reactive murine cytotoxic T lymphocyte clone AHIII12.2, recognizes murine H-2D(b) complexed with peptide p1027 (FAPGVFPYM), as well as human HLA-A2.1 complexed with peptide p1049 (ALWGFFPVL). A commonly proposed model (the molecular mimicry model) used to explain TCR cross-reactivity suggests that the molecular surfaces of the recognized complexes are similar in shape, charge, or both, in spite of the primary sequence differences. To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and D(b)/p1027 to 2.5 Å and 2.8 Å resolution, respectively. The crystal structures show that the TCR footprint regions of the two class I complexes are significantly different in shape and charge. We propose that rather than simple molecular mimicry, unpredictable arrays of common and differential contacts on the two class I complexes are used for their recognition by the same TCR. |
format | Text |
id | pubmed-2192988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21929882008-04-16 Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry Zhao, Rui Loftus, Douglas J. Appella, Ettore Collins, Edward J. J Exp Med Articles The T cell receptor (TCR), from a xeno-reactive murine cytotoxic T lymphocyte clone AHIII12.2, recognizes murine H-2D(b) complexed with peptide p1027 (FAPGVFPYM), as well as human HLA-A2.1 complexed with peptide p1049 (ALWGFFPVL). A commonly proposed model (the molecular mimicry model) used to explain TCR cross-reactivity suggests that the molecular surfaces of the recognized complexes are similar in shape, charge, or both, in spite of the primary sequence differences. To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and D(b)/p1027 to 2.5 Å and 2.8 Å resolution, respectively. The crystal structures show that the TCR footprint regions of the two class I complexes are significantly different in shape and charge. We propose that rather than simple molecular mimicry, unpredictable arrays of common and differential contacts on the two class I complexes are used for their recognition by the same TCR. The Rockefeller University Press 1999-01-18 /pmc/articles/PMC2192988/ /pubmed/9892618 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 Zhao, Rui Loftus, Douglas J. Appella, Ettore Collins, Edward J. Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry |
title | Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry |
title_full | Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry |
title_fullStr | Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry |
title_full_unstemmed | Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry |
title_short | Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry |
title_sort | structural evidence of t cell xeno-reactivity in the absence of molecular mimicry |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192988/ https://www.ncbi.nlm.nih.gov/pubmed/9892618 |
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