title: Comparison of the roles of CD8 alpha alpha and CD8 alpha beta in interaction with MHC class I.
abstract: The CD8 molecule is expressed either as an alpha/alpha homodimer or an alpha/beta heterodimer on thymocytes and cytotoxic T cells, and functions as a coreceptor in concert with TCR for binding the MHC class I/peptide complex. Although CD8alpha/beta heterodimers have been shown to be more effective coreceptors, the precise role of the beta-chain in TCR-mediated thymic maturation and T cell activation is not understood. To understand the role of CD8beta in mediating CD8/MHC class I interaction, we examined whether cell surface CD8alpha/beta heterodimer promotes better cell-cell adhesion with MHC class I than the CD8alpha/alpha homodimer. The abilities of different forms of CD8 to adhere to MHC class I were measured with a cell-cell binding assay. Using a wild-type CD8beta and -alpha, we found that CD8alphabeta heterodimers did not mediate greater cell-cell adhesion than CD8alphaalpha homodimers. Furthermore, we found that chimeric CD8beta-alpha homodimers afforded no detectable binding. These results do not support the idea that CD8alphabeta binding to MHC class I is greater than that of CD8alphaalpha. Rather, they point to an alternative explanation in which CD8beta may play an role in promoting CD8/TCR interaction and/or in signaling/regulatory pathways.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: P B
authors.initials: PB
authors.lastname: Kavathas
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D002448:Cell Adhesion / Q000276:immunology; D019281:Dimerization; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011485:Protein Binding / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000502:physiology
chemical_list: D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D011993:Recombinant Fusion Proteins; D001613:beta 2-Microglobulin