Mother-to-child transmission of HIV infection and CTL escape through HLA-A2-SLYNTVATL epitope sequence variation

Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV inf ection. Evasion of the immune response by CTL escape is associated with pro gression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful co ntrol of viraemia. In order to test this hypothesis, escape through the dom inant HLA-A2-restricted CTL epitope SLYNTVATL (p17 Gag residues 77-85 SL9) in the setting of mother-to-child-transmission (MTCT) was investigated. Ini tial data from two families in which the HIN-infected mother expressed HLA- A*0201 and had transmitted the virus to other family members were consisten t with this hypothesis. In addition, analysis of the gag sequence phylogeny in one family demonstrated that CTL escape variants can be successfully tr ansmitted both horizontally and vertically. To test the hypothesis further, a larger cohort of transmitting mothers (n = 8) and non-transmitters (n = 14) were studied. Variation within the SL9 epitope was associated with expr ession of HLA-A2 (P = 0.04) but overall no clear link between variation fro m the SL9 consensus sequence and MTCT was established. However, the high le vel of background diversity within p17 Gag served to obscure any possible a ssociation between escape and MTCT. In conclusion, these studies highlighte d the obstacles to demonstrating CTL escape arising at this particular epit ope. Alternative strategies likely to be more definitive are discussed. (C) 2001 Published by Elsevier Science B.V.