A Five-Residue HIV Envelope Helper T Cell Determinant: Does This Peptide–MHC Interaction Leave the Binding Groove Half Empty?

Abstract

High-resolution structures have revealed major pockets in the MHC class II peptide binding groove within a region designated P1–P9. The region can accommodate 9-mer peptides, consistent with the observation that minimal core helper T (Th) cell determinants are usually eight or nine residues in size. Here we describe mouse Th cell hybridomas that are specific for a core peptide of only five residues (NPIIL) in the HIV envelope glycoprotein. Effective Th cell stimulation requires that these MHC class II Ia^b-presented peptides contain amino acids flanking the minimal pentamer, but the flanking residues may be located on either the N or C terminus. To explain these findings, we suggest that mini-Th cell epitopes may effectively associate with MHC when only five (or possibly fewer) of the P1–P9 positions are filled. The remaining positions may be empty, or may be associated with a second, perhaps unrelated, peptide moiety.