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rdf:type |
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lifeskim:mentions |
umls-concept:C0003320,
umls-concept:C0005149,
umls-concept:C0023418,
umls-concept:C0040113,
umls-concept:C0085358,
umls-concept:C0181687,
umls-concept:C0456387,
umls-concept:C0567416,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1514562,
umls-concept:C1706438,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C2003941,
umls-concept:C2698600
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pubmed:issue |
8
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pubmed:dateCreated |
2002-4-8
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/CD8 antigen, alpha chain,
http://linkedlifedata.com/resource/pubmed/chemical/CD8alphabeta antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Complementarity Determining Regions,
http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/H-2Kb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/beta 2-Microglobulin,
http://linkedlifedata.com/resource/pubmed/chemical/thymus-leukemia antigens
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
168
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3881-6
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pubmed:dateRevised |
2008-2-27
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pubmed:meshHeading |
pubmed-meshheading:11937542-Amino Acid Sequence,
pubmed-meshheading:11937542-Amino Acid Substitution,
pubmed-meshheading:11937542-Animals,
pubmed-meshheading:11937542-Antigens, CD8,
pubmed-meshheading:11937542-Antigens, Neoplasm,
pubmed-meshheading:11937542-COS Cells,
pubmed-meshheading:11937542-Complementarity Determining Regions,
pubmed-meshheading:11937542-Dimerization,
pubmed-meshheading:11937542-H-2 Antigens,
pubmed-meshheading:11937542-Immune Sera,
pubmed-meshheading:11937542-Membrane Glycoproteins,
pubmed-meshheading:11937542-Mice,
pubmed-meshheading:11937542-Molecular Sequence Data,
pubmed-meshheading:11937542-Mutagenesis, Site-Directed,
pubmed-meshheading:11937542-Peptide Fragments,
pubmed-meshheading:11937542-Protein Binding,
pubmed-meshheading:11937542-Protein Structure, Secondary,
pubmed-meshheading:11937542-Protein Structure, Tertiary,
pubmed-meshheading:11937542-Thymus Gland,
pubmed-meshheading:11937542-Transfection,
pubmed-meshheading:11937542-beta 2-Microglobulin
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pubmed:year |
2002
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Department of Laboratory Medicine and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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