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 through variation in the epitope regions of viral proteins such as a gag. We report here an analysis of variant epitope peptides in three gag epitopes presented by HLA B8. Fifteen variant peptides were examined for their binding to HLA-B8; all but one bound at concentrations comparable to known epitopes. All except two of those that bound could be recognized by CTL from an HLA-B8 positive HIV-1-infected patient and were therefore immunogenic. However, in a hemophiliac patient studied in detail, there was a failure to respond to two immunogenic peptide epitopes representing virus present as provirus in the patient's peripheral blood. In one case, the patient's CTL had previously responded to the peptide; in the other case, there was a good response to a peptide of closely related sequence. Thus there was a selective failure of the CTL response to some proviral epitopes. This impaired reaction to new variants could contribute to the loss of immune control of the infection.
McAdam
S
S
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Klenerman
P
P
Tussey
L
L
Rowland-Jones
S
S
Lalloo
D
D
Phillips
R
R
Edwards
A
A
Giangrande
P
P
Brown
A L
AL
Gotch
F
F
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000276:immunology / Q000378:metabolism; D014644:Genetic Variation; D015488:HIV Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology; D015795:HLA-B8 Antigen / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D011533:Proviruses / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D015795:HLA-B8 Antigen