Brander C, Frahm N, Sango K, Adams S, Pae E, Cohen D, Wurcel A, Walker BD, Marincola F; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).
Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. ThOrA1392.
Massachusetts General Hospital, Boston, United States
Background: HLA classI alleles which share HLA binding motif characteristics can present promiscuously binding CTL epitopes. HLA alleles associated with slow or fast HIV disease progression can also share promiscuous epitopes. Such epitopes can help to address what role the epitope itself plays in determining the rate of HIV disease progression. Methods: 80 HIV-infected individuals were tested for CTL responses against a set of almost 200 optimally defined, HIV CTL epitopes, restricted by more than 60 different HLA classI alleles by IFN-g Elispot. Results: Individuals expressing HLA-B63 (consisting of the B*1516 and B*1517 sub-types) reacted frequently with epitopes that were previously described as HLA-B57 and B58 epitopes and which fulfill the binding motifs for B63 as well as B57/58. Similarly, HLA-B27 restricted epitopes were found to be frequently recognized by HLA-B27 negative, B15 positive individuals presenting with low HIV viral load. Sequence based HLA-subtyping of these alleles is in progress. Conclusion Our data demonstrate that specific HLA-B15 subtype alleles can share CTL epitopes that have previously been described to be restricted by HLA-B57/58 and B27, respectively. The results also show that HLA-B63 presents B57/58 restricted epitopes and is associated with low HIV viral loads in untreated individuals. Furthermore, HLA-B27 restricted epitopes can be presented by at least some additional sub-types of HLA-B15 which may also be associated with relative protection from HIV disease progression. These data point towards an important role of the presented epitope in determining the rate of HIV disease progression. However, structural similarities between the different HLA molecules presenting these shared epitopes may also contribute to the more favorable outcome of HIV infection in subjects expressing these B15 alleles. Further studies will be needed to assess their relative contribution to the control of HIV replication in vivo.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Alleles
- Epitopes
- HIV Infections
- HIV Seropositivity
- HLA-B Antigens
- HLA-B15
- HLA-B27 Antigen
- HLA-B57
- T-Lymphocytes, Cytotoxic
- genetics
- immunology
Other ID:
UI: 102280615
From Meeting Abstracts