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Figure A.11.1 (A) Peptide-binding motifs for DRB1*1501, DRB5*0101, and DRB1*0401. Note that not all of the anchor amino acids outlined in the SYFPEITHI Web site are listed here. For example, for HLA-DR1*0401, see Vogt et al. (1994). (B) Anchor motifs in an immunodominant area of MBP (amino acids 83 to 99).

Figure A.11.1 (A) Peptide-binding motifs for DRB1*1501, DRB5*0101, and DRB1*0401. Note that not all of the anchor amino acids outlined in the SYFPEITHI Web site are listed here. For example, for HLA-DR1*0401, see Vogt et al. (1994). (B) Anchor motifs in an immunodominant area of MBP (amino acids 83 to 99).

Peptide Binding Motifs for MHC Class I and II Molecules

MHC Class II: HLA-DR2 (DRB1*1501; DRB5*0101) and HLA-DR4 (DRB1*0401)

MBP has previously been shown to induce experimental allergic encephalomyelitis (EAE), a well-examined animal model for multiple sclerosis (MS), in several rodent strains (Martin et al., 1992). This protein is used as an example to show potential epitopes that might be recognized by human CD4+ T cells in the context of MS-associated HLA-DR alleles, most notably HLA-DRB1*1501, HLA-DRB5*0101, and an allele found in MS patients with different ethnic backgrounds (i.e., DRB1*0401; Martin et al., 1991; Vogt et al., 1994; Muraro et al., 1997; Smith et al., 1998). Figure A1I.1 depicts the peptide-binding motifs for DRB1*1501, DRB5*0101 (Vogt et al., 1994), and DRB1*0401 (Hammer et al., 1995), and demonstrates where anchor motifs can be found in an immunodominant area of the protein (amino acids 83 to 99). Thus, the presence of DR-binding motifs for three disease-associated DR alleles forms a prerequisite for their high-affinity binding to the respective DR al-leles, and explains why this area of MBP is immunodominant in the context of DRB1*1501, DRB5*0101, and DRB1*0401 (Valli et al., 1993; Vergelli et al., 1997). The HLA binding motifs can easily be retrieved from the SYFPEITHI Web site (see Internet Resources).

Compiled lists of HLA class I and class II anchor motifs, as well as peptide sequences that have been eluted from specific HLA alleles and then sequenced, and peptides that were specifically recognized by T cell clones in the context of a specific HLA allele are listed in the Web sites in Internet Resources.

Literature Cited

Altuvia, Y., Sette, A., Sidney, J., Southwood, S., and Margalit, H. 1997. A structure-based algorithm to predict potential binding peptides to MHC molecules with hydrophobic binding pockets. Hum. Immunol. 58:1-11.

Bjorkman, P.J., Saper, M.A., Samraoui, B., Bennett, W.S., Strominger, J.L., and Wiley, D.C. 1987. Structure of the human class I histocompatibility antigen HLA-A2. Nature 329:506-512.

Brown, J.H., Jardetzky, T.S., Gorga, J.C., Stern, L.J., Urban, R.G., Strominger, J.L., and Wiley, D.C. 1993. Three-dimensional structure of the human

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