The major homology region (MHR) of HIV-1 is a highly conserved 18 amino-acid segment close to the carboxyl-terminus of the capsid protein (p24, residues 155–172). The crystal structure of p24 suggests a dimeric complex with the amino-terminus lying external to the virion core as a five-coiled helix [1]. The carboxyl-terminus also follows an α-helical conformation [2] and is thought to be critical in virion assembly: substitutions or deletions in the MHR abrogate viral particle formation and replication [3–5]. The MHR is conserved among most avian and mammalian retroviruses and is virtually identical between different HIV-1 clades, HIV-2 and simian immunodeficiency virus [6]. Variation at a single residue separates clades B and D from other HIV-1 clades, namely tyrosine at position 169 (clades B and D) rather than phenylalanine (clades A and C). If immunogenic, such a conserved region is a prime candidate for inclusion in subunit vaccines.

Increasing evidence suggests that cytotoxic T lymphocytes (CTL) are important in the control of HIV infection [7]. The MHR contains three previously identified CTL epitopes: an HLA-B14-restricted CTL response was minimally defined as residues 166–174, an HLA-CW8 epitope was localized to residues 173–182, and an HLA-A* 2402-restricted epitope was mapped to residues 163–172 [8–11]. Here we describe four further immunodominant CTL epitopes within the MHR and propose that the MHR should be considered in recombinant subunit vaccine design.