Linked Life Data

11238647

Source:http://linkedlifedata.com/resource/pubmed/id/11238647

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-3-12
pubmed:abstractText
KRN T cells can recognize two self MHC alleles with differing biological consequences. They respond to the foreign peptide RN(42--56) bound to I-A(k) or alternatively initiate autoimmune arthritis by interacting with a self Ag, GPI(282--294), on I-A(g7). Five surface amino acid differences between the two MHC molecules collectively alter which peptide side chains are recognized by the KRN TCR. In this study, it is shown that mutation of only two of these residues, alpha 65 and beta 78, in I-A(k) to their I-A(g7) counterparts is sufficient to allow recognition of the TCR contacts from GPI(282--294). To provide a detailed mechanism for the specificity change, the distinct contributions of each of these two mutations to the global effect on peptide specificity were analyzed. The alpha65 mutation is shown to broaden the spectrum of amino acids permissible at P8 of the peptide. In contrast, the beta 78 mutation alone blocks KRN TCR interaction with I-A(k) and requires the simultaneous presence of the alpha 65 mutation to preserve recognition. In the presence of the alpha 65 mutation, the beta 78 residue broadens peptide recognition at P3 and prevents recognition of the P8 L in RN(42--56), thus producing the observed specificity shift. These results localize the functionally relevant differences between the surfaces of two self-restricted MHC molecules to two residues that have counterbalanced positive and negative contributions to interaction with a single TCR. They highlight how subtle structural distinctions attributable to single amino acids can stand at the interface between foreign Ag responsiveness and pathogenic autoreactivity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4005-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11238647-Amino Acid Sequence, pubmed-meshheading:11238647-Amino Acid Substitution, pubmed-meshheading:11238647-Animals, pubmed-meshheading:11238647-Autoantigens, pubmed-meshheading:11238647-Cell Line, pubmed-meshheading:11238647-Epitopes, T-Lymphocyte, pubmed-meshheading:11238647-Glucose-6-Phosphate Isomerase, pubmed-meshheading:11238647-Histocompatibility Antigens Class II, pubmed-meshheading:11238647-Mice, pubmed-meshheading:11238647-Mice, Inbred AKR, pubmed-meshheading:11238647-Mice, Inbred C57BL, pubmed-meshheading:11238647-Mice, Inbred NOD, pubmed-meshheading:11238647-Mice, Transgenic, pubmed-meshheading:11238647-Molecular Sequence Data, pubmed-meshheading:11238647-Mutagenesis, Site-Directed, pubmed-meshheading:11238647-Peptides, pubmed-meshheading:11238647-Protein Binding, pubmed-meshheading:11238647-Receptors, Antigen, T-Cell, pubmed-meshheading:11238647-Surface Properties, pubmed-meshheading:11238647-T-Lymphocytes
pubmed:year
2001
pubmed:articleTitle
Two MHC surface amino acid differences distinguish foreign peptide recognition from autoantigen specificity.
pubmed:affiliation
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.