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- To study the critical amino acids of both TCR and MHC that interact with peptide P18-I10 of HIV-1 IIIB, the authors used a series of mutant substituted peptides. Peptides substituted with Ala at various positions showed that positions 322R, 324F and 327I were essential for binding to H2-Dd. Residue 325V was critical for interacting with TCR. By employing D-amino acid derived peptides as mutants in order to avoid charge, size and molecular weight differences, they also show that 325V is necessary for CTL-induced cytotoxic activity. Using two distinct CTL clones and molecular modeling they determined that TCR sequences of CDR1 and not CDR3 critically interact with 325V.
- This 10-residue minimally active peptide lies within the immunodominant epitope, RIQRGPGRAFVTIGK, that belongs to gp160, the hypervariable region of Env. Substituted peptides used in this study were RGPGRAFiTI, RGPGRAFlTI, RGPGRAFaTI, RGPGRAFyTI, RGPGRAFfTI, RGPGRAFhTI, RGPGRAFtTI, RGPGRAFsTI, RGPGRAFeTI,RGPGRAFkTI, RGPGRAFrTI and RGPGRAFpTI. In addition, D-amino acid variants of the residues in parentheses were used - (r)GPGRAFVTI, RG(p)GRAFVTI, RGPG(r)AFVTI, RGPGR(a)FVTI, RGPGRA(f)VTI, RGPGRAF(v)TI, RGPGRAFV(t)I, RGPGRAFVT(i), RGPGRAF(i)TI, RGPGRAF(l)TI, RGPGRAF(a)TI, RGPGRAF(y)TI, RGPGRAF(f)TI, RGPGRAF(h)TI and RGPGRAF(t)TI.
Yohko Nakagawa, Hiroto Kikuchi, and Hidemi Takahashi. Molecular Analysis of TCR and Peptide/MHC Interaction Using P18-I10-Derived Peptides with a Single D-Amino Acid Substitution. Biophys. J., 92(7):2570-2582, 1 Apr 2007. PubMed ID: 17208967.
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