High degree of inter-clade cross-reactivity of HIV-1-specific T cell responses at the single peptide level

Abstract

Viral epitopes within regions of low HIV-1 clade B diversity and high inter-clade homology can be recognized in the clade A, B and C variants and indicate a wide degree of cross-isolate and cross-clade recognition by HIV-1-specific T cells. These regions may therefore be of particular relevance for the design of HIV-1 vaccines.

Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications

“…In support of this strategy, promising broad cross-clade cellular immunity against specific HIV-1 epitopes has been described (27,45,51,133); however, only a few epitopes are conserved across different subtypes, and single amino acid substitutions are selected by the CTL immune pressure, allowing the virus to escape with a dramatic deterioration of clinical conditions (8,9). Moreover, several studies have identified sequence variability within, as well as proximal to, characterized optimal epitopes, which can either modulate binding to the HLA molecule, reduce the binding affinity to the cognate T-cell receptor, or interfere with efficient antigen processing, resulting in escape from CTL surveillance (4,14,31,71).…”

Clade-Specific Evolution Mediated by HLA-B*57/5801 in Human Immunodeficiency Virus Type 1 Clade A1 p24

“…While CD8 ϩ T-cell cross-clade recognition has been tested extensively (6,11,19,36,48), few studies have addressed the possibility of clade-specific escape from CD8 ϩ T-cell responses. This may be especially relevant where clade consensus sequences differ in immunologically relevant epitopes.…”

Recognition of Escape Variants in ELISPOT Does Not Always Predict CD8 + T-Cell Recognition of Simian Immunodeficiency Virus-Infected Cells Expressing the Same Variant Sequences

“…The extent to which vaccine-induced CD8 ϩ T cells recognize variants is a crucial question when measuring the ability of vaccine-induced CD8 ϩ T cells to recognize likely challenge viruses-frequent cross-recognition of variant epitopes would suggest that a single vaccine construct might elicit responses effective against diverse viral isolates. Encouragingly, gamma interferon (IFN-␥) enzyme-linked immunospot (ELISPOT) assays indicate that CD8 ϩ T cells generated by both vaccination (23,32) and infection (9,11,12,15,24,30,38,39) often recognize sequences derived from multiple clades of HIV. ELISPOT and intracellular cytokine stain (ICS) assays typically involve stimulating T cells with purified peptides though, bypassing processing and trafficking steps which must occur in an infected cell for a class I MHC molecule to successfully present peptides.…”