The TCR's sensitivity to self peptide–MHC dictates the ability of naive CD8+ T cells to respond to foreign antigens
| Autor: | Ananda W. Goldrath, Yan Xing, Sara E. Hamilton, J Adam Best, Ross B. Fulton, Stephen C. Jameson, Kristin A. Hogquist |
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| Rok vydání: | 2014 |
| Předmět: |
Immunology
Receptors Antigen T-Cell Mice Transgenic chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes CD5 Antigens Major histocompatibility complex Autoantigens Article Major Histocompatibility Complex Antigen hemic and lymphatic diseases Animals Homeostasis Immunology and Allergy Cytotoxic T cell Antigen-presenting cell Mice Knockout biology Gene Expression Profiling T-cell receptor CD28 hemic and immune systems Flow Cytometry Natural killer T cell Specific Pathogen-Free Organisms Mice Inbred C57BL Phenotype biology.protein Female CD8 |
| Zdroj: | Nature Immunology. 16:107-117 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/ni.3043 |
| Popis: | The strength with which complexes of self peptide and major histocompatibility complex (MHC) proteins are recognized by the T cell antigen receptor (TCR) dictates the homeostasis of naive CD8(+) T cells, but its effect on reactivity to foreign antigens is controversial. As expression of the negative regulator CD5 correlates with self-recognition, we studied CD5(lo) and CD5(hi) naive CD8(+) T cells. Gene-expression characteristics suggested CD5(hi) cells were better poised for reactivity and differentiation than were CD5(lo) cells, and we found that the CD5(hi) pool also exhibited more efficient clonal recruitment and expansion, as well as enhanced reactivity to inflammatory cues, during the recognition of foreign antigen. However, the recognition of complexes of foreign peptide and MHC was similar for both subsets. Thus, CD8(+) T cells with higher self-reactivity dominate the immune response to foreign antigens, with implications for T cell repertoire diversity and autoimmunity. |
| Databáze: | OpenAIRE |
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