Hypervariable epitope construct: a synthetic immunogen that overcomes MHC restriction of antigen presentation

Vaccines are not universal in their ability to induce favorable immune resp onses in all individuals because the major histocompatibility complex (MHC) molecules needed for presentation of vaccine components to T cells are lim ited in the peptides they recognize and bind. A heterogeneous cocktail of r elated peptides synthesized simultaneously and representing amino acids 414 -434 of the SIV envelope protein was used to induce immune responses strong er than those induced by a single T cell peptide synthesized conventionally and representing the same region of the viral envelope. The heterogeneous peptide mixture called a hypervariable epitope construct (HEC) was capable of overcoming MHC restriction in peptide presentation in four different inb red mouse strains, including a strain that was a poor responder to the AA 4 14-434 single sequence peptide (SSP). HEC induced proliferation responses 1 5 times better than those induced by SSP. Antibodies elicited by HEC but no t SSP immunization effectively bind viral antigen. The 414-434 HEC and the 414-434 SSP were also tested for their ability to upregulate the expression of MHC class I molecules on the surface of the mutant RMA-S murine cell li ne. Surface display of MHC molecules was measured by confocal microscopy fo llowed by calculation of fluorescence intensity of images. HECs upregulated expression of MHC molecules 30% more than SSP peptides. Our findings sugge st that HEC cocktails could be effective components of subunit vaccines to help overcome the unresponsiveness observed in outbred animals and in human s as a result of MHC-restricted antigen presentation. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.