HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors.
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-gamma 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.
Migueles
S A
SA
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Department of Transfusion Medicine, Clinical Center, and Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sabbaghian
M S
MS
Shupert
W L
WL
Bettinotti
M P
MP
Marincola
F M
FM
Martino
L
L
Hallahan
C W
CW
Selig
S M
SM
Schwartz
D
D
Sullivan
J
J
Connors
M
M
D000483:Alleles; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000276:immunology; D020276:HIV Long-Term Survivors; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000821:virology; D010455:Peptides / Q000378:metabolism; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D014779:Virus Replication; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016655:HIV Core Protein p24; D015235:HLA-B Antigens; D007371:Interferon-gamma; D037181:Lectins, C-Type; D010455:Peptides; D012367:RNA, Viral; D000099192:CD69 Antigens