The HLA system and the immune response to HIV

CD8 T cells recognize "their" antigen (peptide) in context with HLA class I molecules on antigen-presenting cells, whereas CD4 T cells require the presentation of antigenic peptides in context with HLA class II molecules. The generation of an HIV-specific immune response is therefore dependent on the individual HLA pattern.

Antigen-presenting cells may bind HIV peptides in different ways within "grooves" on the HLA class I molecules. Therefore, CD8 T cells can be activated in an optimal or suboptimal way or may not be activated at all. Using large cohorts of HIV-1 infected patients, in whom the natural course of disease (fast versus slow progression) is known, HLA patterns were identified that were associated with a slow versus fast disease progression. These studies suggest that the HLA type could be responsible for the benign course of disease in about 40% of patients with a long-term non-progressive course of disease. Homozygosity for HLA Bw4 is regarded as being protective. Patients who display heterozygosity at the HLA class I loci characteristically show a slower progression of immunodeficiency than patients with homozygosity at these loci (59). An initial study by Kaslow in 1996 demonstrated that HLA B14, B27, B51, B57 and C8 are associated with a slow disease progression, however, the presence of HLA A23, B37 and B49 were associated with the rapid development of immunodeficiency (60). All patients with HLA B35 had developed symptoms of AIDS after 8 years of infection. More recent studies suggest that discordant couples with a "mismatch" at the HLA class I have a protective effect towards heterosexual transmission (61).

In vitro studies in HLA B57-positive patients demonstrate that these patients display HLA B57-restricted CTL directed against HIV-1 peptides. However, it is possible that the identification of protective HLA alleles or HLA-restricted peptides in HIV-1-infected patients with a benign course of disease does not necessarily indicate that the same alleles or peptides are crucial for the design of a protective vaccine. Kaul and co-workers were able to show that CD8 T cells from HIV-1-exposed but uninfected African women recognize different epitopes than CD8 T cells from HIV-1-infected African women (62). This suggests that the epitopes, that the immune system is directed against during a natural infection, might be different from those that are protective against infection.

HLA class II antigens are crucial for the development of an HIV-1-specific CD4 T cell response. Rosenberg (1997) was the first to show that HIV-1-infected patients with a long-term non-progressive course of disease had HIV-1-specific CD4 T cells that could proliferate against HIV-1 antigens (63). The identification of protective or unfavorable HLA class II alleles is less well elaborated than the knowledge about protective HLA class I alleles. Cohorts of vertically infected children and HIV-infected adults demonstrate a protective effect of HLA DR13 (64).

KIR receptors ("Killer cell immunoglobulin like receptors") represent ligands that bind to HLA class I antigens and by functioning as either activating or inhibiting receptors they regulate the activation status of NK cells. Polymorphisms of KIR genes were shown to correlate with slow or rapid progression of HIV disease, especially when the analysis includes known HLA class I polymorphisms (65).

In summary, various genetic polymorphisms have been identified that have an impact on the course of HIV disease. However, there is currently no rationale to recommend routine testing of individual patients or to base therapeutic decisions on genetic testing.

Was this article helpful?

0 0
How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book

Post a comment