TY - JOUR
T1 - HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors
AU - Migueles, Stephen A.
AU - Sabbaghian, M. Shirin
AU - Shupert, W. Lesley
AU - Bettinotti, Maria P.
AU - Marincola, Francesco M.
AU - Martino, Lisa
AU - Hallahan, Clair W.
AU - Selig, Sara M.
AU - Schwartz, David
AU - Sullivan, John
AU - Connors, Mark
PY - 2000/3/14
Y1 - 2000/3/14
N2 - A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4+ T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0.001]. Antigen-specific CD8+ T cells were enumerated by flow cytometric detection of intracellular IFN-γ, in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8+ T cell responses were observed between B*57+ LTNP and five B*57+ progressors (P = 0.4). Although similar frequencies of peptide specific CD8+ T cells were also found, the gag- specific CD8+ T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57+ LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.
AB - A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4+ T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0.001]. Antigen-specific CD8+ T cells were enumerated by flow cytometric detection of intracellular IFN-γ, in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8+ T cell responses were observed between B*57+ LTNP and five B*57+ progressors (P = 0.4). Although similar frequencies of peptide specific CD8+ T cells were also found, the gag- specific CD8+ T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57+ LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.
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U2 - 10.1073/pnas.050567397
DO - 10.1073/pnas.050567397
M3 - Article
C2 - 10694578
AN - SCOPUS:0034646143
SN - 0027-8424
VL - 97
SP - 2709
EP - 2714
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -