Despite multiple, repeated exposures to HIV, some individuals never seroconvert or show any sign of infection. A variety of mechniasms are suggested to be associated with this condition, including HIV specific cell mediated and humoral immune resposnes, as well as mutations affecting receptors for virus entry.
HLAB57 gene: In the late 1990s, researchers showed that a high percentage of people who were naturally immune to HIV (about 1 in 200 infected persons) carry a gene called HLA B57. Interestingly people who carry this gene are also more likely to develop autoimmune disorders. A group of researchers at the new Ragon Institute also showed that individuals with the HLAB57 gene produced larger numbers of killer T cells that can attack more then one epitope associated with HIV (e.g., they cross-react). This makes them more effective against mutant HIV virions which typically are able to escape the immune system.
The basis for this ability of killer T cells to cross react apparently has to do with T cell development in the thymus. In T cell development, those T cells which react strongly with self peptides are eliminated. This is a normal process which prevents T cells from getting into the periphery which could then get activated by self-proteins and cause autoimmunity. People with the HLAB57 protein present fewer self-peptides than most other HLA proteins. Because these individuals’ T cells are presented with fewer self-peptides in the thymus, T cells with receptors that mediate strong binding to viral proteins via just a few important contacts are more likely to escape the thymus. This makes the T cells more cross-reactive to targeted HIV peptide mutants. Unfortunately this also explains why these people have autoimmune problems.
Homozigous deletion (delta32) with the CCR5 receptor gene: are resistant to R5 HIV strains.
IgA-mediated humoral immunity: IgA from HIV-uninfected exposed seronegative individuals (ESN) neutralize in vitro primary strains of HIV-1. Pastori (J Biological Regulators and Homeostatic AG, 2000, Jan-Mar, 14(1), 15-21) analyzed the epitopes of HIV recognized by serum HIV specific IgA of ESN individuals and showed that neutralization of primary HIV strains is mediated by the recognition of gp41 epitopes. Interestingly, IgA of HIV+ individuals recognized different epitopes expressed both within gp120 and gp41.