Comparison of the roles of CD8 alpha alpha and CD8 alpha beta in interaction with MHC class I

• Published in: The Journal of immunology (1950) Vol. 159; no. 12; pp. 6077 - 6082
• Main Authors: Sun, J, Kavathas, PB
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-12-1997
• Subjects: Animals; beta 2-Microglobulin - physiology; CD8 Antigens - biosynthesis; CD8 Antigens - genetics; CD8 Antigens - metabolism; CD8 Antigens - physiology; Cell Adhesion - immunology; COS Cells; Dimerization; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class I - physiology; Humans; Protein Binding - immunology; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - chemistry; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.159.12.6077

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.