Role of CD8beta domains in CD8 coreceptor function: importance for MHC I binding, signaling, and positive selection of CD8+ T cells in the thymus

R Bosselut; S Kubo; T Guinter; J L Kopacz; J D Altman; L Feigenbaum; A Singer

doi:10.1016/s1074-7613(00)80193-4

Role of CD8beta domains in CD8 coreceptor function: importance for MHC I binding, signaling, and positive selection of CD8+ T cells in the thymus

Immunity. 2000 Apr;12(4):409-18. doi: 10.1016/s1074-7613(00)80193-4.

Authors

R Bosselut¹, S Kubo, T Guinter, J L Kopacz, J D Altman, L Feigenbaum, A Singer

Affiliation

¹ Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

PMID: 10795739
DOI: 10.1016/s1074-7613(00)80193-4

Abstract

The contribution of the CD8beta subunit to CD8 coreceptor function is poorly understood. We now demonstrate that the CD8beta extracellular domain increases the avidity of CD8 binding to MHC I, and that the intracellular domain of CD8beta enhances association with two intracellular molecules required for TCR signal transduction, Lck and LAT. By assessing CD8+ T cell differentiation in CD8beta-deficient mice reconstituted with various transgenic CD8beta chimeric molecules, we also demonstrate that the intracellular and extracellular domains of CD8beta can contribute independently to CD8+ T cell development, but that both CD8beta domains together are most efficient. Thus, this study identifies the molecular functions of the CD8beta intracellular and extracellular domains and documents their contributions to CD8+ T cell development.

Publication types

Comparative Study

MeSH terms

Adaptor Proteins, Signal Transducing*
Animals
CD8 Antigens / chemistry
CD8 Antigens / genetics
CD8 Antigens / immunology*
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology*
Carrier Proteins / physiology
Cell Lineage
Clonal Deletion*
Histocompatibility Antigens Class I / physiology
Humans
Lymphocyte Activation / physiology*
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology
Membrane Proteins*
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Phosphoproteins / physiology
Protein Binding
Protein Structure, Tertiary
Receptors, Antigen, T-Cell / immunology*
Recombinant Fusion Proteins / immunology
Signal Transduction
Specific Pathogen-Free Organisms
Structure-Activity Relationship
Thymus Gland / cytology*
Thymus Gland / immunology

Substances

Adaptor Proteins, Signal Transducing
CD8 Antigens
Carrier Proteins
Histocompatibility Antigens Class I
LAT protein, human
Lat protein, mouse
Membrane Proteins
Phosphoproteins
Receptors, Antigen, T-Cell
Recombinant Fusion Proteins
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)