T cell responses in HIV type 1-infected adolescent minorities share similar epitope specificities with whites despite significant differences in HLA class I alleles

被引:17
作者
Bansal, A
Sabbaj, S
Edwards, BH
Ritter, D
Perkins, C
Tang, J
Szinger, JJ
Weiss, H
Goepfert, PA
Korber, B
Wilson, CM
Kaslow, RA
Mulligan, MJ
机构
[1] Univ Alabama, Dept Med, Sch Med, Birmingham, AL 35294 USA
[2] Los Alamos Natl Lab, Los Alamos, NM 87545 USA
[3] Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA
[4] Univ Alabama, Sch Med, Dept Microbiol, Birmingham, AL 35294 USA
[5] Univ Alabama, Sch Med, Dept Pediat, Birmingham, AL 35294 USA
关键词
D O I
10.1089/088922203322588378
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页码:1017 / 1026
页数:10
相关论文
共 24 条
[1]   The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals [J].
Addo, MM ;
Altfeld, M ;
Rosenberg, ES ;
Eldridge, RL ;
Philips, MN ;
Habeeb, K ;
Khatri, A ;
Brander, C ;
Robbins, GK ;
Mazzara, GP ;
Goulder, PJR ;
Walker, BD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (04) :1781-1786
[2]   Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load [J].
Addo, MM ;
Yu, XG ;
Rathod, A ;
Cohen, D ;
Eldridge, RL ;
Strick, D ;
Johnston, MN ;
Corcoran, C ;
Wurcel, AG ;
Fitzpatrick, CA ;
Feeney, ME ;
Rodriguez, WR ;
Basgoz, N ;
Draenert, R ;
Stone, DR ;
Brander, C ;
Goulder, PJR ;
Rosenberg, ES ;
Altfeld, M ;
Walker, BD .
JOURNAL OF VIROLOGY, 2003, 77 (03) :2081-2092
[3]   Vpr is preferentially targeted by CTL during HIV-1 infection [J].
Altfeld, M ;
Addo, MM ;
Eldridge, RL ;
Yu, XG ;
Thomas, S ;
Khatri, A ;
Strick, D ;
Phillips, MN ;
Cohen, GB ;
Islam, SA ;
Kalams, SA ;
Brander, C ;
Goulder, PJR ;
Rosenberg, ES ;
Walker, BD .
JOURNAL OF IMMUNOLOGY, 2001, 167 (05) :2743-2752
[4]   Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations [J].
Cao, K ;
Hollenbach, J ;
Shi, XJ ;
Shi, WX ;
Chopek, M ;
Fernández-Viña, MA .
HUMAN IMMUNOLOGY, 2001, 62 (09) :1009-1030
[5]   HLA and HIV-1:: Heterozygote advantage and B*35-Cw*04 disadvantage [J].
Carrington, M ;
Nelson, GW ;
Martin, MP ;
Kissner, T ;
Vlahov, D ;
Goedert, JJ ;
Kaslow, R ;
Buchbinder, S ;
Hoots, K ;
O'Brien, SJ .
SCIENCE, 1999, 283 (5408) :1748-1752
[6]   Peripheral blood mononuclear cell markers in antiretroviral therapy-naive HIV-infected and high risk seronegative adolescents [J].
Douglas, SD ;
Rudy, B ;
Muenz, L ;
Moscicki, AB ;
Wilson, CM ;
Holland, C ;
Crowley-Nowick, P ;
Vermund, SH .
AIDS, 1999, 13 (13) :1629-1635
[7]   Magnitude of functional CD8+ T-cell responses to the Gag protein of human immunodeficiency virus type 1 correlates inversely with viral load in plasma [J].
Edwards, BH ;
Bansal, A ;
Sabbaj, S ;
Bakari, J ;
Mulligan, MJ ;
Goepfert, PA .
JOURNAL OF VIROLOGY, 2002, 76 (05) :2298-2305
[8]   Differential narrow focusing of immunodominant human immunodeficiency virus Gag-specific cytotoxic T-lymphocyte responses in infected African and Caucasoid adults and children [J].
Goulder, PJR ;
Brander, C ;
Annamalai, K ;
Mngqundaniso, N ;
Govender, U ;
Tang, Y ;
He, S ;
Hartman, KE ;
O'Callaghan, CA ;
Ogg, GS ;
Altfeld, MA ;
Rosenberg, ES ;
Cao, H ;
Kalams, SA ;
Hammond, M ;
Bunce, M ;
Pelton, SI ;
Burchett, SA ;
McIntosh, K ;
Coovadia, HM ;
Walker, BD .
JOURNAL OF VIROLOGY, 2000, 74 (12) :5679-5690
[9]  
Hendel H, 1999, J IMMUNOL, V162, P6942
[10]   Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents [J].
Holland, CA ;
Ellenberg, JH ;
Wilson, CM ;
Douglas, SD ;
Futterman, DC ;
Kingsley, LA ;
Moscicki, AB .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2000, 16 (10) :959-963