Scott Southwood

Identification of Conserved HIV-1-Derived Helper T Lymphocyte Epitopes Using Synthetic Peptides and High Throughput Binding Assays

Human immunodeficiency virus type 1 (HIV-1) infection is marked by a gradual loss of CD4+ T lymphocytes and a specific loss or failure to develop functional HIV-1-specific helper T cells (HTL) in the majority of chronically infected individuals. However, there is also mounting evidence that HTL that are reactive against HIV-1 antigens may play an important role in delaying disease progression. The development of vaccines to induce protective or therapeutic cellular immune responses to HIV-1 has been attempted, but it is complicated by the presence of numerous viral variants [1], Epitope-based vaccines offer the advantage of focusing immune responses on multiple conserved epitopes. One potential obstacle to the development of epitope-based vaccines has been the large degree of polymorphism of HLA molecules. Previous studies have demonstrated that the majority of HLA class I and class II molecules can be grouped in broad supertypes with overlapping peptide binding specificity [2]. In the case of the HLA-DR molecules, a single superfamily encompassing DRB1 alleles expressed in the majority of humans has been defined [3]. Based on these data, we have been investigating an HIV-1 vaccine construct that includes multiple, conserved CTL and HTL epitopes. A number of broadly cross-reactive minimal CTL epitopes in conserved regions of HIV-1 proteins have been identified. By contrast, relatively few HIV-1-specific HTL epitopes have been identified. We have, therefore, sought to identify conserved, major histocompatibility complex (MHC) class II-restricted epitopes in HIV-1 that would be recognized by a large fraction of the global population.