Structure-based Design and Evaluation of MHC Class II Binding Peptides

Quantitative Structure−Activity Relationship of Peptides Binding to the Class II Major Histocompatibility Complex Molecule AqAssociated with Autoimmune Arthritis

“…25 Moreover, Jane-wit et al have postulated a common autoimmune-motif (KXXS) for peptides binding to H-2q MHC class II molecule(s) based on comparisons of peptides responsible for eliciting experimental autoimmune myocarditis. 28 Various complementary methods for designing and generating peptides to elucidate binding and/or subsequent T-cell responses are available, including scanning of single amino acids, 20,29 use of positional scanning combinatorial libraries, [30][31][32] phage-display libraries, 33,34 peptide isosteres, 25,35 and computational methods such as structure-based design 34,36 and statistical molecular design (SMD). 37,38 There has been great effort in predicting binding of short peptides to MHC molecules.…”

Contribution of peptides to multiple sclerosis research

“…The use of overlapping 16-mer MAG peptides led for the first time to the identification of MAG(97-112) as a T-cell and encephalitogenic epitope in ABH mice able to induce EAE. Immunization of SJL mice with MAG peptides failed to induce the disease, whereas immunization of SJL mice with synthetic peptides of OSP induced major T-cell responses in particular to OSP (73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88) and OSP (81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96). However, while immunization of ABH mice with OSP revealed the two immunodominant T-cell epitopes OSP (49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)…”

“…63 Lipoconjugation of peptide Ags enhances immunoadjuvant effects in an in vitro system by using CD4þ T cells. Pam-GpMBP (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) and [Lys 75 (Pam)]-GpMBP(74-85) induced increased T-cell responsiveness compared with the native nonlipidated peptide. On the other hand, lipoderivatives of GpMBP(82-98) did not increase the T-cell response, demonstrating that the superagonist inducing effect of lipoconjugation is epitope-specific.…”

“…76 Therefore, structural information regarding binding of peptides to MHC II molecules is extremely important for the design of compounds involved in MHC-peptide-TCR complex interaction. De Haan et al 77 described the construction of a homology model of MHC II molecules and binding of the peptide that are involved in EAE. The validity of the model was investigated using experimental data of biotinylated GpMBP (72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) binding to such MHC molecules.…”

“…108 Conformational properties of the epitope MBP(74-85) (QKSQRSQDENPV), which can initiate EAE, were investigated by semiempirical methods. Energy calculations were carried out on MBP (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) 109 To provide rational elements to design APLs, de Haan et al 110 The synthesis of the cyclo(75-82)MBP (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) analogue conjugated to mannan via (Lys-Gly) 5 linker was recently reported. 111 However, to date, no biological data have been reported for this compound.…”