PMID: 7547702May 1, 1995Paper

Interactions among polymorphic and conserved residues in MHC class II proteins affect MHC-peptide conformation and T cell recognition

International Immunology
K M TateP P Jones

Abstract

The structural basis for MHC-restricted T cell recognition of the N-terminal peptide of myelin basic protein (MBP Ac1-11) presented by two mouse class II alleles, Ak and Au, was examined, focusing on the roles of A beta chain polymorphic residues 38 beta (in the beta sheet) and 61 beta (in the alpha helix) in controlling the responses of panels of Ak- and Au-restricted T cell hybridomas. Despite the conservative nature of the substitutions at 38 beta (k = Val, u = Leu) and 61 beta (k = Trp, u = Tyr), transfectants expressing Ak or Au proteins carrying allelic substitutions at 38 beta and/or 61 beta gave dramatically reduced T cell responses. The modest reduction in peptide binding detected using a biotinylated MBP peptide analog appear insufficient to explain the reduced responses, suggesting that changes at 38,61 beta create conformational changes in the MHC-peptide complex. The impact of allelic substitutions at 38,61 beta on T cell responses is also modulated by other residues differing between Ak and Au. To explore the structural basis for these phenomena, protein models were developed of the Ak, Au and 38,61 beta mutant proteins using self-consistent ensemble optimization methodologies. Substitutions of the alternative all...Continue Reading

Citations

Oct 17, 2001·Toxicon : Official Journal of the International Society on Toxinology·K N SrinivasanV Brusic
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·C Lee, H M McConnell
Aug 1, 1996·The Journal of Experimental Medicine·C BeesonH M McConnell
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·J D RabinowitzH M McConnell
Jul 16, 2015·Journal of Industrial Microbiology & Biotechnology·Etsu Tashiro, Masaya Imoto
Sep 25, 2018·Bioscience, Biotechnology, and Biochemistry·Masaya Imoto
Jul 17, 2015·Archives of Pharmacal Research·Estu Tashiro, Masaya Imoto
Sep 11, 2017·Molecular Neurobiology·Nicole N M TragerCraig C Beeson

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