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Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus.

Publication ,  Journal Article
Shinzawa, M; Moseman, EA; Gossa, S; Mano, Y; Bhattacharya, A; Guinter, T; Alag, A; Chen, X; Cam, M; McGavern, DB; Erman, B; Singer, A
Published in: Nature immunology
May 2022

T cell specificity and function are linked during development, as MHC-II-specific TCR signals generate CD4 helper T cells and MHC-I-specific TCR signals generate CD8 cytotoxic T cells, but the basis remains uncertain. We now report that switching coreceptor proteins encoded by Cd4 and Cd8 gene loci functionally reverses the T cell immune system, generating CD4 cytotoxic and CD8 helper T cells. Such functional reversal reveals that coreceptor proteins promote the helper-lineage fate when encoded by Cd4, but promote the cytotoxic-lineage fate when encoded in Cd8-regardless of the coreceptor proteins each locus encodes. Thus, T cell lineage fate is determined by cis-regulatory elements in coreceptor gene loci and is not determined by the coreceptor proteins they encode, invalidating coreceptor signal strength as the basis of lineage fate determination. Moreover, we consider that evolution selected the particular coreceptor proteins that Cd4 and Cd8 gene loci encode to avoid generating functionally reversed T cells because they fail to promote protective immunity against environmental pathogens.

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Published In

Nature immunology

DOI

EISSN

1529-2916

ISSN

1529-2908

Publication Date

May 2022

Volume

23

Issue

5

Start / End Page

731 / 742

Related Subject Headings

  • Thymus Gland
  • Receptors, Antigen, T-Cell
  • Immunology
  • Cell Lineage
  • Cell Differentiation
  • CD8-Positive T-Lymphocytes
  • CD8 Antigens
  • CD4-Positive T-Lymphocytes
  • CD4 Antigens
  • 3204 Immunology
 

Citation

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Shinzawa, M., Moseman, E. A., Gossa, S., Mano, Y., Bhattacharya, A., Guinter, T., … Singer, A. (2022). Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus. Nature Immunology, 23(5), 731–742. https://doi.org/10.1038/s41590-022-01187-1
Shinzawa, Miho, E Ashley Moseman, Selamawit Gossa, Yasuko Mano, Abhisek Bhattacharya, Terry Guinter, Amala Alag, et al. “Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus.Nature Immunology 23, no. 5 (May 2022): 731–42. https://doi.org/10.1038/s41590-022-01187-1.
Shinzawa M, Moseman EA, Gossa S, Mano Y, Bhattacharya A, Guinter T, et al. Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus. Nature immunology. 2022 May;23(5):731–42.
Shinzawa, Miho, et al. “Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus.Nature Immunology, vol. 23, no. 5, May 2022, pp. 731–42. Epmc, doi:10.1038/s41590-022-01187-1.
Shinzawa M, Moseman EA, Gossa S, Mano Y, Bhattacharya A, Guinter T, Alag A, Chen X, Cam M, McGavern DB, Erman B, Singer A. Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus. Nature immunology. 2022 May;23(5):731–742.

Published In

Nature immunology

DOI

EISSN

1529-2916

ISSN

1529-2908

Publication Date

May 2022

Volume

23

Issue

5

Start / End Page

731 / 742

Related Subject Headings

  • Thymus Gland
  • Receptors, Antigen, T-Cell
  • Immunology
  • Cell Lineage
  • Cell Differentiation
  • CD8-Positive T-Lymphocytes
  • CD8 Antigens
  • CD4-Positive T-Lymphocytes
  • CD4 Antigens
  • 3204 Immunology