Modulating Cathepsin Cleavage Sites in HIV gp120 Envelope Protein Alters the Cellular Immune Response

Friday, November 08, 2013 — Poster Session IV
2:00 p.m. – 4:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NCI	IMMUNO-6

Authors

B.F. Frey
Y Sui
A H
Y W
P.W. Berman
J.A. Berzofsky

Abstract

A major goal in HIV vaccine development is identifying antigens that are capable of eliciting long-term, protective antibody and cellular responses. Limited success with native recombinant HIV gp120 proteins suggested altering antigen processing as an approach to improve the immunogenicity of the HIV gp120 protein. Here, we have utilized recombinant HIV gp120 proteins with mutations at the cathepsin S site (T322T323) and D cleavage site (L181Y182) within the HIV gp120 protein. Cathepsins S and D are important human proteases that play critical roles in antigen processing. In these studies, we have found that altering the cathepsin S digestion site in a minimal epitope IGPGRAFYTT from T322T323 to V322V323 improved CD8+ T cell recognition of this epitope in the V3 domain. We are currently determining if the mechanism behind the enhanced response is the result of increased binding affinity due to changing the anchor residue with the MHC I molecule, or prevented degradation of the minimal epitope, or both. Furthermore, we are investigating the effects of antigen processing and MHC class II presentation to CD4+ T cells. These results suggest that antigen processing plays an important role in immunogenicity. We speculate that HIV may exploit antigen processing to escape recognition.