IMMUNOGENIC HIV VARIANT PEPTIDES THAT BIND TO HLA-B8 CAN FAIL TO STIMULATE CYTOTOXIC T-LYMPHOCYTE RESPONSES

Cytotoxic T lymphocyte responses in HIV infection can be impaired thro ugh variation in the epitope regions of viral proteins such as gag. We report here an analysis of variant epitope peptides in three gag epit opes presented by HLA B8. Fifteen variant peptides were examined for t heir binding to HLA-B8; all but one bound at concentrations comparable to known epitopes. All except two of those that bound could be recogn ized by CTL from an HLA-B8 positive HIV-l-infected patient and were th erefore immunogenic. However, in a hemophiliac patient studied in deta il, there was a failure to respond to two immunogenic peptide epitopes representing virus present as provirus in the patient's peripheral bl ood. In one case, the patient's CTL had previously responded to the pe ptide; in the other case, there was a good response to a peptide of cl osely related sequence. Thus there was a selective failure of the CTL response to some proviral epitopes. This impaired reaction to new vari ants could contribute to the loss of immune control of the infection.