Bansal Anju, Sabbaj Steffanie, Edwards Bradley H, Ritter Doug, Perkins Christopher, Tang James, Szinger James J, Weiss Heidi, Goepfert Paul A, Korber Bette, Wilson Craig M, Kaslow Richard A, Mulligan Mark J
Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
AIDS Res Hum Retroviruses. 2003 Nov;19(11):1017-26. doi: 10.1089/088922203322588378.
African-Americans (AFAM) and Hispanics (HIS) represent only 13% and 12% of the U.S. population but 54% and 19%, respectively, of annually incident HIV-1 infections in the United States. The 88 patients in the current study were from U.S. racial or ethnic minority groups (72% African-American, 17% Hispanic), female (85%), and adolescent (mean age 20 years). Their HLA allele distributions were distinct from patterns in U.S. whites. Overall, HIV-1-specific T cell responses were observed in 91% of participants: 75% recognized peptides in Gag, 67% Pol, 57% Nef, and 41% Env. The patients recognized 87 (36%) of 244 Gag, Pol, Env, or Nef peptides tested. Similar to what has been seen in white cohorts, epitope-rich peptide clusters were identified within conserved functional domains in Gag matrix, Gag capsid, Pol reverse transcriptase, and Nef. Peptides representing variable regions from within the B subtype or with more changes from the B subtype consensus sequence were less likely to stimulate a positive T cell response. A small percentage (17%) of unique T cell responses was found in this cohort that displayed no previously known T cell epitopes. Dominant responses generally overlapped with epitope-rich regions in HIV-1 described previously for whites, although many of these peptides were likely restricted by HLA class I alleles not previously associated with these epitopes. Hence host genetic variation among different racial groups may have less impact on the utility of candidate HIV-1 vaccines than previously suspected.
非裔美国人(AFAM)和西班牙裔(HIS)在美国人口中分别仅占13%和12%,但在美国每年新感染HIV-1的病例中分别占54%和19%。本研究中的88名患者来自美国的种族或族裔少数群体(72%为非裔美国人,17%为西班牙裔),均为女性(85%),且为青少年(平均年龄20岁)。他们的HLA等位基因分布与美国白人的模式不同。总体而言,91%的参与者观察到了HIV-1特异性T细胞反应:75%的人识别Gag中的肽段,67%识别Pol,57%识别Nef,41%识别Env。患者识别了所检测的244种Gag、Pol、Env或Nef肽段中的87种(36%)。与白人队列中所见情况类似,在Gag基质、Gag衣壳、Pol逆转录酶和Nef的保守功能域内鉴定出了富含表位的肽簇。代表B亚型可变区或与B亚型共有序列变化更多的肽段刺激阳性T细胞反应的可能性较小。在该队列中发现了一小部分(17%)独特的T细胞反应,这些反应未显示出先前已知的T细胞表位。优势反应通常与先前针对白人描述的HIV-1中富含表位的区域重叠,尽管其中许多肽段可能受先前未与这些表位相关联的HLA I类等位基因限制。因此,不同种族群体之间的宿主基因变异对候选HIV-1疫苗效用的影响可能比先前怀疑的要小。