Molecular analysis of the same HIV peptide functionally binding to both a class I and a class II MHC molecule

• Published in: The Journal of immunology (1950) Vol. 154; no. 4; pp. 1973 - 1986
• Main Authors: Takeshita, T, Takahashi, H, Kozlowski, S, Ahlers, JD, Pendleton, CD, Moore, RL, Nakagawa, Y, Yokomuro, K, Fox, BS, Margulies, DH
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.1995
• Subjects: Amino Acid Sequence; Animals; Binding, Competitive; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line; Epitopes - immunology; H-2 Antigens - immunology; H-2 Antigens - metabolism; Histocompatibility Antigen H-2D; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV-1 - immunology; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Peptide Fragments - immunology; Peptide Fragments - metabolism; Protein Binding; Protein Conformation; Sequence Alignment; Structure-Activity Relationship
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.154.4.1973

Although several peptides have been found to bind to both class I and class II molecules, the basis for this binding of the same peptide to two classes of MHC molecules has not been compared previously. We have analyzed one such peptide, P18 from the V3 loop of HIV-1 gp160, which we have previously shown to be recognized by CD8+ CTL with the class I molecule H-2Dd, and by CD4+ Th cells with the class II molecule I-Ad. With the use of truncated and substituted peptides, we found that the minimal core peptides are very similar, that the residues required for class I binding precisely fit the recently identified consensus motif for peptides binding to Dd (XGPX[R/K/H]XXX(X) [L/I/F]), and that at least three of the same residues are involved in binding to class II I-Ad. In addition, several of the same residues are involved in TCR interaction when the peptide is presented by class I and class II molecules. Modeling shows results to be consistent with the crystal structure of a peptide-class II MHC complex. Thus, the recognition of this versatile peptide by CD4+ Th cells with class II MHC molecules and by CD8+ cytotoxic T cells with class I MHC molecules is remarkably similar in both the core peptide used and the role of different residues in the ternary complex.