Participation of CD4 coreceptor molecules in T-cell repertoire selection

During thymocyte development, progenitor cells bearing both CD4 and CD8 coreceptor molecules mature into functional T lymphocytes that express these proteins in a mutually exclusive way. Although T-cell specificity is determined primarily by the structure of the T-cell antigen receptor (TCR) heterod...

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Bibliographic Details
Published in:Nature (London) 1991-01, Vol.349 (6306), p.241-243
Main Authors: Teh, Hung-Sia, Garvin, Alex M, Forbush, Katherine A, Carlow, Douglas A, Davis, Craig B, Littman, Dan R, Perlmutter, Roger M
Format: Article
Language:English
Subjects:
Alloantigens
Animals
Antibodies, Monoclonal
Antigens
Antigens, Differentiation, T-Lymphocyte - biosynthesis
Bearing
Biological and medical sciences
CD4 antigen
CD4 Antigens - physiology
CD8 antigen
CD8 Antigens
Cells (biology)
Cellular biology
Clonal selection
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Regulation
Genetics
H-2 Antigens - physiology
H-Y Antigen - immunology
Histocompatibility Antigen H-2D
Histocompatibility Antigens Class I - physiology
Immunity (Disease)
Immunobiology
Lymphatic system
Lymphocytes
Lymphocytes T
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Maturation
Medical research
Mice
Mice, Transgenic
Molecules
Positive selection
Progenitor cells
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell, alpha-beta
Recombinant Fusion Proteins
Rodents
Stem cells
T cell receptors
T-Lymphocytes - immunology
T-Lymphocytes, Regulatory - immunology
Thymocytes
Transgenic animals
Transgenic mice
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Summary:During thymocyte development, progenitor cells bearing both CD4 and CD8 coreceptor molecules mature into functional T lymphocytes that express these proteins in a mutually exclusive way. Although T-cell specificity is determined primarily by the structure of the T-cell antigen receptor (TCR) heterodimer, a developmentally regulated process acts to ensure that cells bearing class II-restricted TCRs are CD4+ and those bearing class I-restricted TCRs express only CD8. To investigate this maturation process, we have engineered transgenic mice in which CD4 is expressed in all thymocyte subsets and in all peripheral T cells. Peripheral CD4+8+ T lymphocytes from these mice react with both class I and class II alloantigens. Moreover, expression of the CD4 transgene disrupts the positive selection of doubly transgenic thymocytes bearing a class I-restricted TCR specific for the male (H-Y) antigen. Hence the CD4 coreceptor participates directly in T-cell repertoire selection.
ISSN:0028-0836
1476-4687
DOI:10.1038/349241a0