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The complementarity-determining region-like loops of CD8 alpha interact differently with beta 2-microglobulin of the class I molecules H-2Kb and thymic leukemia antigen, while similarly with their alpha 3 domains.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Apr 15; Vol. 168 (8), pp. 3881-6. - Publication Year :
- 2002
-
Abstract
- The murine CD8 glycoprotein interacts with both classical MHC class I molecules and some nonclassical molecules, including the thymic leukemia Ag (TL). TL binds preferentially to CD8alphaalpha homodimers with a 10-fold higher affinity than H-2K(b) class I molecules. To understand the molecular basis for this difference, we created a panel of CD8alpha mutants and tested the ability of the CD8alphaalpha homodimers to bind to H-2K(b) tetramers and TL tetramers. Mutations in three CD8 residues located on the complementarity-determining region-like loops contacting the negatively charged loop in the alpha3 domain of MHC class I greatly reduced binding to both tetramers. Because TL and H-2K(b) class I sequences are highly conserved in the alpha3 domain of MHC class I, this suggests that CD8 contacts the alpha3 domain of TL and H-2K(b) in a similar manner. In contrast, mutations in residues on the A and B beta strands of CD8 that are involved in contact with beta(2)-microglobulin affected interaction with the H-2K(b) tetramer, but not the TL tetramer. Therefore, the orientation of interaction of TL with CD8 appears to be different from that of H-2K(b). The unique high affinity binding of TL with CD8alphaalpha is most likely a result of amino acid differences in the alpha3 domain between TL and H-2K(b), particularly at positions 198 (K to D) and 228 (M to T), which are contact residues in the CD8alphaalpha-H-2K(b) cocrystal.
- Subjects :
- Amino Acid Sequence
Amino Acid Substitution genetics
Amino Acid Substitution immunology
Animals
CD8 Antigens genetics
CD8 Antigens immunology
COS Cells
Complementarity Determining Regions metabolism
Dimerization
Immune Sera metabolism
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
Peptide Fragments immunology
Peptide Fragments metabolism
Protein Binding genetics
Protein Binding immunology
Protein Structure, Secondary genetics
Protein Structure, Tertiary genetics
Thymus Gland immunology
Thymus Gland metabolism
Transfection
Antigens, Neoplasm metabolism
CD8 Antigens metabolism
H-2 Antigens metabolism
Membrane Glycoproteins metabolism
beta 2-Microglobulin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 168
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 11937542
- Full Text :
- https://doi.org/10.4049/jimmunol.168.8.3881