Frahm Nicole, Adams Sharon, Kiepiela Photini, Linde Caitlyn H, Hewitt Hannah S, Lichterfeld Mathias, Sango Kaori, Brown Nancy V, Pae Eunice, Wurcel Alysse G, Altfeld Marcus, Feeney Margaret E, Allen Todd M, Roach Timothy, St John M Anne, Daar Eric S, Rosenberg Eric, Korber Bette, Marincola Francesco, Walker Bruce D, Goulder Philip J R, Brander Christian
Partners AIDS Research Center, Massachusetts General Hospital, No. 5214, 149 13th Street, Charlestown, MA 02129, USA.
J Virol. 2005 Aug;79(16):10218-25. doi: 10.1128/JVI.79.16.10218-10225.2005.
Several HLA class I alleles have been associated with slow human immunodeficiency virus (HIV) disease progression, supporting the important role HLA class I-restricted cytotoxic T lymphocytes (CTL) play in controlling HIV infection. HLA-B63, the serological marker for the closely related HLA-B1516 and HLA-B1517 alleles, shares the epitope binding motif of HLA-B57 and HLA-B58, two alleles that have been associated with slow HIV disease progression. We investigated whether HIV-infected individuals who express HLA-B63 generate CTL responses that are comparable in breadth and specificity to those of HLA-B57/58-positive subjects and whether HLA-B63-positive individuals would also present with lower viral set points than the general population. The data show that HLA-B63-positive individuals indeed mounted responses to previously identified HLA-B57-restricted epitopes as well as towards novel, HLA-B63-restricted CTL targets that, in turn, can be presented by HLA-B57 and HLA-B58. HLA-B63-positive subjects generated these responses early in acute HIV infection and were able to control HIV replication in the absence of antiretroviral treatment with a median viral load of 3,280 RNA copies/ml. The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection.
几种HLA I类等位基因与人类免疫缺陷病毒（HIV）疾病进展缓慢相关，这支持了HLA I类限制性细胞毒性T淋巴细胞（CTL）在控制HIV感染中发挥的重要作用。HLA-B63是密切相关的HLA-B1516和HLA-B1517等位基因的血清学标志物，与HLA-B57和HLA-B58具有相同的表位结合基序，这两个等位基因都与HIV疾病进展缓慢有关。我们调查了表达HLA-B63的HIV感染者产生的CTL反应在广度和特异性上是否与HLA-B57/58阳性受试者相当，以及HLA-B63阳性个体的病毒载量是否也低于普通人群。数据显示，HLA-B63阳性个体确实对先前确定的HLA-B57限制性表位以及新的HLA-B63限制性CTL靶点产生了反应，而这些靶点又可以由HLA-B57和HLA-B58呈递。HLA-B63阳性受试者在急性HIV感染早期就产生了这些反应，并且在没有抗逆转录病毒治疗的情况下能够控制HIV复制，中位病毒载量为3280个RNA拷贝/毫升。这些数据支持了所呈递表位在介导HIV复制的相对控制中的重要作用，并有助于更好地定义HIV感染得到控制的免疫相关因素。
