Role of CD8beta domains in CD8 coreceptor function: importance for MHC I binding, signaling, and positive selection of CD8+ T cells in the thymus.
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.
Bosselut
R
R
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kubo
S
S
Guinter
T
T
Kopacz
J L
JL
Altman
J D
JD
Feigenbaum
L
L
Singer
A
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016827:CD8 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002352:Carrier Proteins / Q000502:physiology; D019070:Cell Lineage; D017637:Clonal Deletion; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D016827:CD8 Antigens; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)