当前位置： SCI文献检索 > AIDS RESEARCH AND HUMAN RETROVIRUSES期刊下所有文献 > Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure.

Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure.

Abstract：

:In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two alleles differ by only three amino acids in regions involved in HLA-peptide recognition. This study evaluated a cohort of over 1000 persons with chronic HIV clade C virus infection to determine whether clinical outcome differences associated with B*5801 (n = 93) and B*5802 ( n = 259) expression are associated with differences in HIV-1-specific CD8 (+) T cell responses. The overall breadth and magnitude of HIV-1-specific CD8(+) T cell responses were lower in persons expressing B*5802, and epitope presentation by B*5802 contributed significantly less to the overall response as compared to B*5801-restricted CD8 (+) T cells. Moreover, viral load in B*5802-positive persons was higher and CD4 cell counts lower when this allele contributed to the overall CD8 (+) T cell response, which was detected exclusively through a single epitope in Env. In addition, persons heterozygous for B*5802 compared to persons homozygous for other HLA-B alleles had significantly higher viral loads. Viral sequencing revealed strong selection pressure mediated through B*5801-restricted responses but not through B*5802. These data indicate that minor differences in HLA sequence can have a major impact on epitope recognition, and that selective targeting of Env through HLA-B*5802 is at least ineffectual if not actively adverse in the containment of viremia. These results provide experimental evidence that not all epitope-specific responses contribute to immune containment, a better understanding of which is essential to shed light on mechanisms involved in HIV disease progression.

journal_name

AIDS Res Hum Retroviruses

journal_title

AIDS research and human retroviruses

authors

Ngumbela KC,Day CL,Mncube Z,Nair K,Ramduth D,Thobakgale C,Moodley E,Reddy S,de Pierres C,Mkhwanazi N,Bishop K,van der Stok M,Ismail N,Honeyborne I,Crawford H,Kavanagh DG,Rousseau C,Nickle D,Mullins J,Heckerman D,K

doi

10.1089/aid.2007.0124

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

72-82

issue

eissn

0889-2229

issn

1931-8405

journal_volume

pub_type

杂志文章

在线工具

Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure.