Eintrag weiter verarbeiten
Different affinity windows for virus and cancer‐specific T‐cell receptors: Implications for therapeutic strategies
Gespeichert in:
| Zeitschriftentitel: | European Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | European Journal of Immunology, 42, 2012, 12, S. 3174-3179 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| Zusammenfassung: | <jats:p><jats:styled-content style="fixed-case">T</jats:styled-content>‐cell destiny during thymic selection depends on the affinity of the <jats:styled-content style="fixed-case">TCR</jats:styled-content> for autologous peptide ligands presented in the context of <jats:styled-content style="fixed-case">MHC</jats:styled-content> molecules. This is a delicately balanced process; robust binding leads to negative selection, yet some affinity for the antigen complex is required for positive selection. All <jats:styled-content style="fixed-case">TCR</jats:styled-content>s of the resulting repertoire thus have some intrinsic affinity for an <jats:styled-content style="fixed-case">MHC</jats:styled-content> type presenting an assortment of peptides. Generally, <jats:styled-content style="fixed-case">TCR</jats:styled-content> affinities of peripheral <jats:styled-content style="fixed-case">T</jats:styled-content> cells will be low toward self‐derived peptides, as these would have been presented during thymic selection, whereas, by serendipity, binding to pathogen‐derived peptides that are encountered de novo could be stronger. A crucial question in assessing immunotherapeutic strategies for cancer is whether natural <jats:styled-content style="fixed-case">TCR</jats:styled-content> repertoires have the capacity for efficiently recognizing tumor‐associated peptide antigens. Here, we report a comprehensive comparison of <jats:styled-content style="fixed-case">TCR</jats:styled-content> affinities to a range of <jats:styled-content style="fixed-case">HLA</jats:styled-content>‐<jats:styled-content style="fixed-case">A</jats:styled-content>2 presented antigens. <jats:styled-content style="fixed-case">TCR</jats:styled-content>s that bind viral antigens fall within a strikingly higher affinity range than those that bind cancer‐related antigens. This difference may be one of the key explanations for tumor immune escape and for the deficiencies of <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell vaccines against cancer.</jats:p> |
|---|---|
| Umfang: | 3174-3179 |
| ISSN: |
0014-2980
1521-4141 |
| DOI: | 10.1002/eji.201242606 |