Development of CD4+T cells expressing a nominally MHC class I-restricted T cell receptor by two different mechanisms
| Autor: | Herman N. Eisen, Jianzhu Chen, Tam Nuygen, Vinay Mahajan, Phillip D. Holler, Qing Ge |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
Mice Knockout Multidisciplinary Histocompatibility Antigens Class I Histocompatibility Antigens Class II Models Immunological Receptors Antigen T-Cell CD1 hemic and immune systems chemical and pharmacologic phenomena Biological Sciences Biology MHC restriction Major histocompatibility complex Molecular biology Cell Line Mice Inbred C57BL Mice Thymocyte MHC class I biology.protein Animals Cytotoxic T cell IL-2 receptor CD8 |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:1822-1827 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Differences in T cell receptor (TCR) signaling initiated by interactions among TCRs, coreceptors, and self-peptide–MHC complexes determine the outcome of CD4 versus CD8 lineage of T cell differentiation. The H-2Ldand Kbm3alloreactive 2C TCR is positively selected by MHC class I Kband a yet-to-be identified nonclassical class I molecule to differentiate into CD8+T cells. Here we describe two mechanisms by which CD4+2C T cells can be generated in 2C TCR-transgenic mice. In the RAG−/−background, development of CD4+2C T cells requires the expression of both I-Aband the TAP genes, indicating that both MHC class I and II molecules are required for positive selection of these T cells. Notably, only some of the 2C+RAG−/−mice (≈30%) develop CD4+2C T cells, with frequencies in individual mice varying from 0.5% to as high as ≈50%. In the RAG+background, where endogenous TCRα genes are rearranged and expressed, CD4+2C T cells are generated because these cells express the 2C TCR as well as additional TCRs, consisting of the 2C TCRβ and endogenous TCRα chains. Similarly, T cells expressing the OT-1 TCR, which is nominally MHC class I-restricted, can also develop into CD4+T cells through the same two mechanisms. Thus, expression of two TCRs by a single thymocyte, TCR recognition of multiple MHC molecules, and heterogeneity of TCR, coreceptors, and peptide–MHC interactions in the thymus all contribute to the outcome of CD4 versus CD8 lineage development. |
| Databáze: | OpenAIRE |
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