PMID: 8986809Dec 24, 1996Paper

Complementary mutations in an antigenic peptide allow for crossreactivity of autoreactive T-cell clones

Proceedings of the National Academy of Sciences of the United States of America
L J AusubelD A Hafler

Abstract

T cells recognize antigen by formation of a trimolecular complex in which the T-cell receptor (TCR) recognizes a specific peptide antigen within the groove of a major histocompatibility complex (MHC) molecule. It has generally been assumed that T-cell recognition of two distinct MHC-antigen complexes is due to similarities in the three-dimensional structure of the complexes. Here we report results of experiments examining the crossreactivity of TCRs recognizing the myelin basic protein peptide MBPp85-99 and several of its analogs in the context of MHC. We demonstrate that single conservative amino acid substitutions of the antigenic peptide at the predominant TCR contact residues at positions 91 and 93 totally abrogate reactivity of specific T-cell clones. Yet, when a conservative substitution is made at position 91 concomitant with a substitution at position 93, the T-cell clones regain reactivity equivalent with that of the original stimulating peptide. Thus, the exact nature of the amino acid side chains engaging one TCR functional pocket may change the apparent selectivity of the other predominant TCR functional pocket, thus suggesting a remarkable degree of receptor plasticity. This ability of the TCR-MHC-peptide complex t...Continue Reading

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Citations

Sep 3, 2008·Journal of Clinical Immunology·Cristina Maria CostantinoDavid A Hafler
Mar 24, 2004·Molecular Immunology·Kai W Wucherpfennig
Dec 1, 1996·Current Opinion in Immunology·D A Hafler, R Flavell
Mar 11, 1998·Current Opinion in Immunology·S Hausmann, K W Wucherpfennig
Nov 6, 1998·The Journal of Experimental Medicine·R L Ufret-VincentyS Brocke
Jan 1, 1997·Acta Neurologica Scandinavica. Supplementum·P Höllsberg
Feb 28, 2002·Journal of Virology·Mary L SpenglerJane Azizkhan-Clifford
Jun 8, 1999·Annual Review of Immunology·K C GarciaI A Wilson
Mar 6, 2002·The Journal of Clinical Investigation·David A Hafler
Jun 21, 2001·Biochemical and Biophysical Research Communications·S FujiiY Nishimura
Jan 5, 2001·Expert Opinion on Investigational Drugs· van Noort JM
Apr 3, 2007·Seminars in Immunology·Kai W WucherpfennigEli E Sercarz
Mar 26, 2005·Immunological Reviews·David A HaflerClare Baecher-Allan
Jul 27, 2000·Seminars in Immunology
May 4, 2001·Journal of Autoimmunity·K W Wucherpfennig
Apr 7, 2004·The Journal of Clinical Investigation·David A Hafler
Dec 6, 2014·Current Rheumatology Reports·William E RuffMartin A Kriegel
Nov 10, 2013·PLoS Computational Biology·Jorg J A CalisBjoern Peters
Oct 4, 2000·Nature Medicine·C P Genain, S S Zamvil
Nov 10, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ivan MascanfroniClaudia G Pellizas
Jul 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A AmraniP Santamaria
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joseph LustgartenClemencia Pinilla
Dec 20, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·P W DudaD A Hafler
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasushi UemuraYasuharu Nishimura
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·B HemmerR Martin
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·D BasuP M Allen
Nov 6, 2021·Science Immunology·Juhi R KuchrooLiliana E Lucca

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