MOLECULAR ANALYSIS OF THE SAME HIV PEPTIDE FUNCTIONALLY BINDING TO BOTH A CLASS-I AND A CLASS-II MHC MOLECULE

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 clas s I molecule H-2D(d), and by CD4(+) Th cells with the class II molecul e I-A(d). With the use of truncated and substituted peptides, we found that the minimal core peptides are very similar, that the residues re quired for class I binding precisely fit the recently identified conse nsus motif for peptides binding to D-d (XGPX[R/K/H]XXX(X)[L/I/F]), and that at least three of the same residues are involved in binding to c lass II I-A(d). 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 crysta l structure of a peptide-class II MHC complex. Thus, the recognition o f this versatile peptide by CD4(+) Th cells with class II MHC molecule s and by CD8(+) cytotoxic T cells with class I MHC molecules is remark ably similar in both the core peptide used and the role of different r esidues in the ternary complex.