HIV and HLA Class I: An Evolving Relationship

Abstract

Successful vaccine development for infectious diseases has largely been achieved in settings where natural immunity to the pathogen results in clearance in at least some individuals. HIV presents an additional challenge in that natural clearance of infection does not occur, and the correlates of immune protection are still uncertain. However, partial control of viremia and markedly different outcomes of disease are observed in HIV infected persons. Here we examine the antiviral mechanisms implicated by one variable that has been consistently associated with extremes of outcome, namely HLA class I alleles, and in particular HLA-B, and examine the mechanisms by which this modulation is likely to occur, and the impact of these interactions on evolution of the virus and the host. Studies to date provide evidence for both HLA-dependent and epitope-dependent influences on viral control and viral evolution, and have important implications for the continued quest for an effective HIV vaccine.

Preexisting CD8 + T-cell immunity to the H7N9 influenza A virus varies across ethnicities

“…Conversely, individuals with HLA-A*0101, A*6801, B*1501, and A*2402 may have little, if any, evidence of established CTL immunity to, for example, the H7N9 virus. Interestingly, HLA1 has been the one parameter repeatedly associated with HIV control, with B57 and B27 being the most protective, whereas the converse is true for B*35 and B*53 (18). Although we have tested preexisting CD8 + T-cell immunity to H7N9 in a vast number (n = 59) of samples (n = 42 for Fig.…”

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

“…Likewise, human host determinants that correlate with protective immunity in genome-wide association studies consistently map to the class I loci of the human leukocyte antigens (HLA) on chromosome 6, further highlighting the crucial role that major histocompatibility complex (MHC) class I-restricted T cells may play in containing viral replication. Particular alleles, including HLA-A*11:01, -B*57:01, and -B27/B*27:05, regularly emerge as correlates of protection for those exposed to or infected by HIV-1 (6,7). The association with lower viral loads and longer survival times supports the premise that particular class I HLA elicit protective antiviral immunity via the selective presentation of HIV-1 ligands.…”

Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells

“…+ T cell responses from study participants were mapped by IFN-γ ELISPOT, using 270 previously defined HIV optimal CD8 + epitopes (74). CD8 + T cell clones against the targeted peptides were established from PBMCs of HIV-infected study participants, as previously described (43).…”